ФИЗИОЛОГИЧЕСКАЯ СИСТЕМА СОЕДИНИТЕЛЬНОЙ ТКАНИ И ОНКОГЕНЕЗ. I. РОЛЬ КЛЕТОЧНЫХ КОМПОНЕНТОВ СТРОМЫ В РАЗВИТИИ ОПУХОЛИ
Ключові слова:
система соединительной ткани, фибробласты, миофибробласты, эндотелиальные клетки, мезенхимальные клетки, звездчатые клетки, экстрацеллюлярный матрикс.Анотація
Обзор представляет современные взгляды на роль системы соединительной
ткани в патогенезе злокачественного роста. С этих позиций обсуждается
значение различных клеточных компонентов соединительной ткани, в частности фибробластов, миофибробластов, эндотелиальных, мезенхимальных
и звездчатых клеток. Рассматривается участие этих клеток в процессе опухолевого роста, возможность изменения приэтом их фенотипических свойств
ифункциональной активности. Отмечается роль некоторых белковых структур экстрацеллюлярного матрикса в развитии опухоли. Параллельно указывается, что каждый из клеточных компонентов в последующем может быть
мишенью для терапии.
Посилання
Богомолец АА. Рак ианергия мезенхимы. В: Общая ичастная онкология, т 1. К: Изд-во АН УССР, 1942: 389–92.
Кавецький РЄ. Роль активної мезенхіми в диспозиції до злоякісних пухлин. К: Изд-во АН УССР, 1937. 213 с.
Богомолец АА. Диалектика онкологии. Нов тер архив 1931; 24 (2): 147–60.
Бережная НМ. Роль клеток системы иммунитета в микроокружении опухоли. Взаимодействие клеток системы иммунитета с другими компонентами микроокружения. Онкология 2009; 11 (2): 86–93.
Soysal SD, Tzankov A, Muenst SE. Role of the tumor microenvironment in breast cancer. Pathobiology 2015; 82 (3–4): 142–52.
Stadler M, Walter S, Walzl A, et al. Increased complexity in carcinomas: Analyzing and modeling the interaction of human cancer cells with their microenvironment. Semin Cancer Biol 2015; 35: 107–24.
Бережная НМ. Семейства интерлейкинов. Биология ионкогенез. К.: Наукова думка, 2013. 576 с.
Чайка ЕИ. О некоторых спорных вопросах учения о физиологической системы соединительной ткани. Цитотоксины в современной медицине, т 2. К.: ДМБ Гос мед из-во УССР, 1960: 30–34.
Langley RR, Fidler IJ. Tumor cell-organ microenvironment interactions in the pathogenesis of cancer metastasis. Endocr Rev 2007; 28 (3): 297–321.
Witz IP. The tumor microenvironment: the making of a paradigm. Cancer Microenviron 2009; 2 (Suppl 1): 9–17.
Benlalam H, Jalil A, Hasmim M, et al. Gap junction communication between autologous endothelial and tumor cells induce cross-recognition and elimination by specific CTL. J Immunol 2009; 182 (5): 2654–64.
Heindryckx F, Gerwins P. Targeting the tumor stroma in hepatocellular carcinoma. World J Hepatol 2015; 7 (2): 165–76.
Brown FD, Turley SJ. Fibroblastic reticular cells: organization and regulation of the T lymphocyte life cycle. J Immunol 2015; 194 (4): 1389–94.
Lukacs-Kornek V, Malhotra D, Fletcher AL, et al. Regulated release of nitric oxide by nonhematopoietic stroma controls expansion of the activated T cell pool in lymph nodes. Nat Immunol 2011; 12 (11): 1096–104.
Bremnes RM, Dønnem T, Al-Saad S, et al. The role of tumor stroma in cancer progression and prognosis: emphasis on carcinoma- 12 associated fibroblasts and non-small cell lung cancer. J Thorac Oncol 2011; 6 (1): 209–17.
Malhotra D, Fletcher AL, Turley SJ. Stromal and hematopoietic cells in secondary lymphoid organs: partners in immunity. Immunol Rev 2013; 251 (1): 160–76.
Mueller KL, Madden JM, Zoratti GL, et al. Fibroblastsecreted hepatocyte growth factor mediates epidermal growth factor receptor tyrosine kinase inhibitor resistance in triple-negative breast cancers through paracrine activation of Met. Breast Cancer Res 2012; 14 (4): R104.
Teichgräber V, Monasterio C, Chaitanya K, et al. Specific inhibition of fibroblast activation protein (FAP)-alpha prevents tumor progression in vitro. Adv Med Sci 2015; 60 (2): 264–72.
Бережная НМ, Чехун ВФ. Иммунология злокачественного роста. К: Наук думка, 2005. 791 с.
Rupp C, Scherzer M, Rudisch A, et al. IGFBP7, a novel tumor stroma marker, with growth-promoting effects in colon cancer through a paracrine tumor-stroma interaction. Oncogene 2015; 34 (7): 815–25.
Esposito I, Menicagli M, Funel N, et al. Inflammatory cells contribute to the generation of an angiogenic phenotype in pancreatic ductal adenocarcinoma. J Clin Pathol 2004; 57 (6): 630–6.
Huang Y, Simms AE, Mazur A, et al. Fibroblast activation protein-α promotes tumor growth and invasion of breast cancer cells through non-enzymatic functions. Clin Exp Metastasis 2011; 28 (6): 567–79.
Tran E, Chinnasamy D, Yu Z, et al. Immune targeting of fibroblast activation protein triggers recognition of multipotent bone marrow stromal cells and cachexia. J Exp Med 2013; 210 (6): 1125–35.
Mishra PJ, Merlino G. A traitor in our midst: mesenchymal stem cells contribute to tumor progression and metastasis. Future Oncol 2008; 4 (6): 745–9.
Van Bockstal M, Lambein K, Van Gele M, et al. Differential regulation of extracellular matrix protein expression in carcinomaassociated fibroblasts by TGF-β1 regulates cancer cell spreading but not adhesion. Oncoscience 2014; 1 (10): 634–48.
De Vlieghere E, Gremonprez F, Verset L, et al. Tumorenvironment biomimetics delay peritoneal metastasis formation by deceiving and redirecting disseminated cancer cells. Biomaterials 2015; 54: 148–57.
Schweiger T, Nikolowsky C, Starlinger P, et al. Stromal expression of heat-shock protein 27 is associated with worse clinical outcome in patients with colorectal cancer lung metastases. PLoS One 2015; 10 (3): e0120724.
Kamińska K, Szczylik C, Bielecka ZF, et al. The role of the cell-cell interactions in cancer progression. J Cell Mol Med 2015; 19 (2): 283–96.
Van Bockstal M, Lambein K, Van Gele M, et al. Differential regulation of extracellular matrix protein expression in carcinomaassociated fibroblasts by TGF-β1 regulates cancer cell spreading but not adhesion. Oncoscience 2014; 1 (10): 634–48.
Orimo A, Weinberg RA. Heterogeneity of stromal fibroblasts in tumors. Cancer Biol Ther 2007; 6 (4): 618–9.
Öhlund D, Elyada E, Tuveson D. Fibroblast heterogeneity in the cancer wound. J Exp Med 2014; 211 (8): 1503–23.
Bruzzese F, Hägglöf C, Leone A, et al. Local and systemic protumorigenic effects of cancer-associated fibroblast-derived GDF15. Cancer Res 2014; 74 (13): 3408–17.
Egeblad M, Littlepage LE, Werb Z. The fibroblastic coconspirator in cancer progression. Cold Spring Harb Symp Quant Biol 2005; 70: 383–8.
Yu Y, Xiao CH, Tan LD, et al. Cancer-associated fibroblasts induce epithelial-mesenchymal transition of breast cancer cells through paracrine TGF-β signalling. Br J Cancer 2014; 110 (3): 724–32.
Chen SF, Nieh S, Jao SW, et al. The paracrine effect of cancer-associated fibroblast-induced interleukin-33 regulates the invasiveness of head and neck squamous cell carcinoma. J Pathol 2013; 231 (2): 180–9.
Chowdhury R, Webber JP, Gurney M, et al. Cancer exosomes trigger mesenchymal stem cell differentiation into pro-angiogenic and pro-invasive myofibroblasts. Oncotarget 2015; 6 (2): 715–31.
Webber JP, Spary LK, Sanders AJ, et al. Differentiation of tumour-promoting stromal myofibroblasts by cancer exosomes. Oncogene 2015; 34 (3): 290–302.
Lecomte J, Masset A, Blacher S, et al. Bone marrowderived myofibroblasts are the providers of pro-invasive matrix
metalloproteinase 13 in primary tumor. Neoplasia 2012; 14 (10): 943–51.
Galván JA, Zlobec I, Wartenberg M, et al. Expression of E-cadherin repressors SNAIL, ZEB1 and ZEB2 by tumour and stromal cells influences tumour-budding phenotype and suggests heterogeneity of stromal cells in pancreatic cancer. Br J Cancer 2015; 112 (12): 1944–50.
Heaphy CM, Gaonkar G, Peskoe SB, et al. Prostate stromal cell telomere shortening is associated with risk of prostate cancer in the placebo arm of the Prostate Cancer Prevention Trial. Prostate 2015; 75 (11): 1160–6.
Lisanti MP, Martinez-Outschoorn UE, Sotgia F. Oncogenes induce the cancer-associated fibroblast phenotype: metabolic symbiosis and «fibroblast addiction» are new therapeutic targets for drug discovery. Cell Cycle 2013; 12 (17): 2723–32.
Su J, Zhang L, Zhang W, et al. Targeting the biophysical properties of the myeloma initiating cell niches: a pharmaceutical synergism analysis using multi-scale agent-based modeling. PLoS One 2014; 9 (1): e85059.
Kunisaki Y. The hematopoietic stem cell niche. Rinsho Ketsueki 2015; 56 (10): 1888–93 (in Japanese).
Borovski T, De Sousa E, Melo F, et al. Cancer stem cell niche: the place to be. Cancer Res 2011; 71 (3): 634–9.
Sottoriva A, Sloot PM, Medema JP, Vermeulen L. Exploring cancer stem cell niche directed tumor growth. Cell Cycle 2010; 9 (8): 1472–9.
Tsuyada A, Chow A, Wu J, et al. CCL2 mediates cross-talk between cancer cells and stromal fibroblasts that regulates breast cancer stem cells. Cancer Res 2012; 72 (11): 2768–79.
Skalli O, Schürch W, Seemayer T, et al. Myofibroblasts from diverse pathologic settings are heterogeneous in their content of actin isoforms and intermediate filament proteins. Lab Invest 1989; 60 (2): 275–85.
Lúcio PS, Cavalcanti AL, Alves PM, et al. Myofibroblasts and their relationship with oral squamous cell carcinoma. Braz J Otorhinolaryngol 2013; 79 (1): 112–8.
Khamis ZI, Iczkowski KA, Sahab ZJ, Sang QX. Protein profiling of isolated leukocytes, myofibroblasts, epithelial, basal, and endothelial cells from normal, hyperplastic, cancerous, and inflammatory human prostate tissues. J Cancer 2010; 1: 70–9.
Brisson BK, Mauldin EA, Lei W, et al. Type III collagen directs stromal organization and limits metastasis in a murine model of breast cancer. Am J Pathol 2015; 185 (5): 1471–86.
Epa AP, Thatcher TH, Pollock SJ, et al. Normal human lung epithelial cells inhibit transforming growth factor-β induced myofibroblast differentiation via prostaglandin E2. PLoS One 2015; 10 (8): e0135266.
Holmberg C, Ghesquière B, Impens F, et al. Mapping proteolytic processing in the secretome of gastric cancer-associated myofibroblasts reveals activation of MMP-1, MMP-2, and MMP3. J Proteome Res 2013; 12 (7): 3413–22.
Lv H, Liu R, Fu J, et al. Epithelial cell-derived periostin functions as a tumor suppressor in gastric cancer through stabilizing p53 and E-cadherin proteins via the Rb/E2F1/p14ARF/Mdm2 signaling pathway. Cell Cycle 2014; 13 (18): 2962–74.
Dayer C, Stamenkovic I. Recruitment of matrix metalloproteinase-9 (MMP-9) to the fibroblast cell surface by lysyl
hydroxylase 3 (LH3) triggers transforming growth factor-β (TGF-β) activation and fibroblast differentiation. J Biol Chem 2015; 290 (22): 13763–78.
Desmoulière A, Guyot C, Gabbiani G. The stroma reaction myofibroblast: a key player in the control of tumor cell behavior. Int J Dev Biol 2004; 48 (5–6): 509–17.
Schmitt-Gräff A, Desmoulière A, Gabbiani G. Heterogeneity of myofibroblast phenotypic features: an example of fibroblastic cell plasticity. Virchows Arch 1994; 425 (1): 3–24.
Ernsting MJ, Hoang B, Lohse I, et al. Targeting of metastasispromoting tumor-associated fibroblasts and modulation of pancreatic tumor-associated stroma with a carboxymethylcellulose-docetaxel nanoparticle. J Control Release 2015; 206: 122–30.
Luksic I, Suton P, Manojlovic S, et al. Significance of myofibroblast appearance in squamous cell carcinoma of the oral cavity on the occurrence of occult regional metastases, distant metastases, and survival. Int J Oral Maxillofac Surg 2015; 44 (9): 1075–80.
Kumar JD, Holmberg C, Kandola S, et al. Increased expression of chemerin in squamous esophageal cancer myofibroblasts and role in recruitment of mesenchymal stromal cells. PLoS One 2014; 9 (7): e104877.
Sobral LM, Bufalino A, Lopes MA, et al. Myofibroblasts in the stroma of oral cancer promote tumorigenesis via secretion of activin A. Oral Oncol 2011; 47 (9): 840–6.
Mehner C, Hockla A, Miller E, et al. Tumor cell-produced matrix metalloproteinase 9 (MMP-9) drives malignant progression and metastasis of basal-like triple negative breast cancer. Oncotarget 2014; 5 (9): 2736–49.
Vered M, Shohat I, Buchner A, Dayan D. Myofibroblasts in stroma of odontogenic cysts and tumors can contribute to variations in the biological behavior of lesions. Oral Oncol 2005; 41 (10): 1028–33.
Ivanov VN, Zhou H, Ghandhi SA, et al. Radiation-induced bystander signaling pathways in human fibroblasts: a role for interleukin-33 in the signal transmission. Cell Signal 2010; 22 (7): 1076–87.
Spary LK, Salimu J, Webber JP, et al. Tumor stromaderived factors skew monocyte to dendritic cell differentiation
toward a suppressive CD14+ PD-L1+ phenotype in prostate cancer. Oncoimmunology 2014; 3 (9): e955331.
Shu H, Li HF. Prognostic effect of stromal myofibroblasts in lung adenocarcinoma. Neoplasma 2012; 59 (6): 658–61.
Friedenstein AJ, Gorskaja JF, Kulagina NN. Fibroblast precursors in normal and irradiated mouse hematopoietic organs. Exp Hematol 1976; 4 (5): 267–74.
Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284 (5411): 143–7.
Weber M, Apostolova G, Widera D, et al. Alternative generation of CNS neural stem cells and PNS derivatives from neural crest-derived peripheral stem cells. Stem Cells 2015; 33 (2): 574–88.
Hoogduijn MJ. Are mesenchymal stromal cells immune cells? Arthritis Res Ther 2015; 17: 88.
Song LX, Guo J, He Q, et al. Study on phenotypic and cytogenetic characteristics of bone marrow mesenchymal stem cells in myelodysplastic syndromes. Zhonghua Xue Ye Xue Za Zhi 2013; 34 (2): 127–32 (in Chinese).
Wagner W, Wein F, Seckinger A, et al. Comparative characteristics of mesenchymal stem cells from human bone marrow, adipose tissue, and umbilical cord blood. Exp Hematol 2005; 33 (11): 1402–16.
Liotta F, Angeli R, Cosmi L, et al. Toll-like receptors 3 and 4 are expressed by human bone marrow-derived mesenchymal stem cells and can inhibit their T-cell modulatory activity by impairing Notch signaling. Stem Cells 2008; 26 (1): 279–89.
Raicevic G, Rouas R, Najar M, et al. Inflammation modifies the pattern and the function of Toll-like receptors expressed by human mesenchymal stromal cells. Hum Immunol 2010; 71 (3): 235–44.
Chen PM, Yen ML, Liu KJ, et al. Immunomodulatory properties of human adult and fetal multipotent mesenchymal stem cells. J Biomed Sci 2011; 18: 49.
Liotta F, Querci V, Mannelli G, et al. Mesenchymal stem cells are enriched in head neck squamous cell carcinoma, correlates with tumour size and inhibit T-cell proliferation. Br J Cancer 2015; 112 (4): 745–54.
Wang X, Lazorchak AS, Song L, et al. Immune modulatory mesenchymal stem cells derived from human embryonic stem cells through a trophoblast-like stage. Stem Cells 2015 Nov 2 [Epub ahead of print].
Prockop DJ. Concise review: two negative feedback loops place mesenchymal stem/stromal cells at the center of early regulators of inflammation. Stem Cells 2013; 31 (10): 2042–6.
Ren G, Zhao X, Zhang L, et al. Inflammatory cytokineinduced intercellular adhesion molecule-1 and vascular cell
adhesion molecule-1 in mesenchymal stem cells are critical for immunosuppression. J Immunol 2010; 184 (5): 2321–8.
Wang Q, Li X, Luo J, et al. The allogeneic umbilical cord mesenchymal stem cells regulate the function of T helper 17 cells from patients with rheumatoid arthritis in an in vitro co-culture system. BMC Musculoskelet Disord 2012; 13: 249.
Nemoto Y, Kanai T, Takahara M, et al. Bone marrowmesenchymal stem cells are a major source of interleukin-7 and sustain colitis by forming the niche for colitogenic CD4 memory T cells. Gut 2013; 62 (8): 1142–52.
Yang ZX, Han ZB, Ji YR, et al. CD106 identifies a subpopulation of mesenchymal stem cells with unique immunomodulatory properties. PLoS One 2013; 8 (3): e59354.
Plumas J, Chaperot L, Richard MJ, et al. Mesenchymal stem cells induce apoptosis of activated T cells. Leukemia 2005; 19 (9): 1597–604.
Ostrand-Rosenberg S, Horn LA, Haile ST. The programmed death-1 immune-suppressive pathway: barrier to antitumor immunity. J Immunol 2014; 193 (8): 3835–41.
Singh MK, Chaudhuri S, Bhattacharya D, et al. T11 target structure induced modulations of the pro-inflammatory and antiinfammatorycytokine expressions in experimental animals for glioma abrogation. Int Immunopharmacol 2015; 24 (2): 198–207.
Lu M, Wu J, He F, et al. Cell expression patterns of CD147 in N-diethylnitrosamine/phenobarbital-induced mouse hepatocellular carcinoma. J Mol Histol 2015; 46 (1): 79–91.
Yang X, Zhai N, Sun M, et al. Influence of lymphatic endothelial cells on proliferation and invasiveness of esophageal carcinoma cells in vitro and lymphangiogenesis in vivo. Med Oncol 2015; 32 (8): 222.
Zhao ZH, Tian Y, Yang JP, et al. RhoC, vascular endothelial growth factor and microvascular density in esophageal squamous cell carcinoma. World J Gastroenterol 2015; 21 (3): 905–12.
Benlalam H, Carré T, Jalil A, et al. Regulation of gap junctions in melanoma and their impact on Melan-A/MART-1-specific CD8+ T lymphocyte emergence. J Mol Med (Berl) 2013; 91 (10): 1207–20.
Song K, Song Y, Zhao XP, et al. Oral cancer/endothelial cell fusion experiences nuclear fusion and acquisition of enhanced survival potential. Exp Cell Res 2014; 328 (1): 156–63.
Bremnes RM, Al-Shibli K, Donnem T, et al. The role of tumorinfiltrating immune cells and chronic inflammation at the tumor site on cancer development, progression, and prognosis: emphasis on nonsmall cell lung cancer. J Thorac Oncol 2011; 6 (4): 824–33.
Xiao L, Kim DJ, Davis CL, et al. Tumor endothelial cells with distinct patterns of TGFβ-driven endothelial-to-mesenchymal transition. Cancer Res 2015; 75 (7): 1244–54.
Lin F, Wang N, Zhang TC. The role of endothelialmesenchymal transition in development and pathological process.
IUBMB Life 2012; 64 (9): 717–23.
Apte MV, Haber PS, Applegate TL, et al. Periacinar stellate shaped cells in rat pancreas: identification, isolation, and culture. Gut 1998; 43 (1): 128–33.
Nielsen MF, Mortensen MB, Detlefsen S. The impact of desmoplasia and pancreatic stellate cells on pancreatic cancer. Ugeskr Laeger 2015; 177 (34): V01150079 (in Danish).
Apte MV, Wilson JS, Lugea A, Pandol SJ. A starring role for stellate cells in the pancreatic cancer microenvironment. Gastroenterology 2013; 144 (6): 1210–9.
Masamune A, Kikuta K, Watanabe T, et al. Hypoxia stimulates pancreatic stellate cells to induce fibrosis and angiogenesis in pancreatic cancer. Am J Physiol Gastrointest Liver Physiol 2008; 295 (4): G709–17.
Zambirinis CP, Levie E, Nguy S, et al. TLR9 ligation in pancreatic stellate cells promotes tumorigenesis. J Exp Med 2015; 212 (12): 2077–94.
Thiery JP. Metastasis: alone or together? Curr Biol 2009; 19 (24): R1121–3.
Mace TA, Bloomston M, Lesinski GB. Pancreatic cancerassociated stellate cells: A viable target for reducing immunosuppressionin the tumor microenvironment. Oncoimmunology 2013; 2 (7): e24891
Apte MV, Xu Z, Pothula S, et al. Pancreatic cancer: The microenvironment needs attention too! Pancreatology 2015; 15 (4 Suppl): S32–8.
Eguchi D, Ikenaga N, Ohuchida K, et al. Hypoxia enhances the interaction between pancreatic stellate cells and cancer cells via increased secretion of connective tissue growth factor. J Surg Res 2013; 181 (2): 225–33.
Apte MV, Haber PS, Darby SJ, et al. Pancreatic stellate
cells are activated by proinflammatory cytokines: implications for
pancreatic fibrogenesis. Gut 1999; 44 (4): 534–41.
Ma T, Wang Z, Yang Z, Chen J. Cluster of differentiation 147 is a key molecule during hepatocellular carcinoma cell-hepatic stellate cell cross-talk in the rat liver. Mol Med Rep 2015; 12 (1): 111–8.
Neuman MG, Sha K, Esguerra R, et al. Inflammation and repair in viral hepatitis C. Dig Dis Sci 2008; 53 (6): 1468–87.
Heindryckx F, Gerwins P. Targeting the tumor stroma in hepatocellular carcinoma. World J Hepatol 2015; 7 (2): 165–76.
Song J, Ge Z, Yang X, et al. Hepatic stellate cells activated by acidic tumor microenvironment promote the metastasis of hepatocellular carcinoma via osteopontin. Cancer Lett 2015; 356 (2 Pt B): 713–20.
Guan J, Zhang H, Wen Z, et al. Retinoic acid inhibits pancreatic cancer cell migration and EMT through the downregulation of IL-6 in cancer associated fibroblast cells. Cancer Lett 2014; 345 (1): 132–9.
Ogden SR, Noto JM, Allen SS. Matrix metalloproteinase-7 and premalignant host responses in Helicobacter pylori-infected mice. Cancer Res 2010; 70 (1): 30–5.
Chuang CK, Pang ST, Chuang TJ, Liao SK. Profiling of matrix metalloproteinases and tissue inhibitors of metalloproteinases proteins in bladder urothelial carcinoma. Oncol Lett 2010; 1 (4): 691–5.
Brisson BK, Mauldin EA, Lei W, et al. Type III collagen directs stromal organization and limits metastasis in a murine model of breast cancer. Am J Pathol 2015; 185 (5): 1471–86.
Multhaupt HA, Leitinger B, Gullberg D, Couchman JR. Extracellular matrix component signaling in cancer. Adv Drug Deliv Rev 2015 Oct 28 [Epub ahead of print].
Allen MD, Marshall JF, Jones JL. αvβ6 Expression in myoepithelial cells: a novel marker for predicting DCIS progression with therapeutic potential. Cancer Res 2014; 74 (21): 5942–7.
Mehner C, Radisky DC. Triggering the landslide: The tumorpromotional effects of myofibroblasts. Exp Cell Res 2013; 319 (11): 1657–62.
Kubow KE, Vukmirovic R, Zhe L, et al. Mechanical forces regulate the interactions of fibronectin and collagen I in extracellular matrix. Nat Commun 2015; 6: 8026.
Kang Y, Georgiou AI, MacFarlane RJ, et al. Fibronectin stimulates the osteogenic differentiation of murine embryonic stem cells. J Tissue Eng Regen Med 2015 [Epub ahead of print].
Rosin NL, Falkenham A, Sopel MJ, et al. Regulation and role of connective tissue growth factor in AngII-induced myocardial fibrosis. Am J Pathol 2013; 182 (3): 714–26.
Sainz B Jr, Alcala S, Garcia E, et al. Microenvironmental hCAP-18/LL-37 promotes pancreatic ductal adenocarcinoma by activating its cancer stem cell compartment. Gut 2015; 64 (12): 1921–35.
