Proinvasive extracellular matrix remodeling for tumor progression
Cancer is a systemic disease in which neoplastic cells interact with multiple types of non-neoplastic stromal cells as well as non-cellular components. The extracellular matrix (ECM) is a non-cellular component that is aberrantly regulated in many types of tumor microenvironments. Since the ECM generally maintains the tissue structure and provides mechanical forces in the tumor microenvironment, it has been simply assumed to act as a physical barrier for cancer metastasis and have a passive role in cancer progression. However, a substantial body of evidence has suggested that ECM remodeling influences many aspects of cancer cell behaviors and its importance has attracted attention in cancer biology. Abnormal ECM affects cancer progression through several ways such as inducing hypoxia, immune cells interaction by promoting mesenchymal shift and cell transformation. Accordingly, in this review we summarize and discusses the role of the ECM in modulating epithelial cells and surrounding stomatal cell components and considers its prospects in cancer biology.
KeywordsExtracellular matrix Metastatic cancer Cancer stem cells Hypoxia Immune cells
This work was supported by the National Research Foundation (NRF) and Ministry of Science, ICT and Future Planning, Korean government, through its National Nuclear Technology Program (2016R1E1A1A01942075).
Compliance with ethical standards
Conflict of interest
All authors declare no conflict of interest.
- Chiavarina B, Whitaker-Menezes D, Migneco G, Martinez-Outschoorn UE, Pavlides S, Howell A, Tanowitz HB, Casimiro MC, Wang C, Pestell RG, Grieshaber P, Caro J, Sotgia F, Lisanti MP (2010) HIF1-alpha functions as a tumor promoter in cancer associated fibroblasts, and as a tumor suppressor in breast cancer cells: autophagy drives compartment-specific oncogenesis. Cell Cycle 9:3534–3551CrossRefGoogle Scholar
- Hall PA, Watt FM (1989) Stem cells: the generation and maintenance of cellular diversity. Development 106:619–633Google Scholar
- Kaplan RN, Riba RD, Zacharoulis S, Bramley AH, Vincent L, Costa C, Macdonald DD, Jin DK, Shido K, Kerns SA, Zhu ZP, Hicklin D, Wu Y, Port JL, Altorki N, Port ER, Ruggero D, Shmelkov SV, Jensen KK, Rafii S, Lyden D (2005) VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 438:820–827CrossRefGoogle Scholar
- Merdad A, Karim S, Schulten HJ, Dallol A, Buhmeida A, Al-Thubaity F, Gari MA, Chaudhary AG, Abuzenadah AM, Al-Qahtani MH (2014) Expression of matrix metalloproteinases (MMPs) in primary human breast cancer: MMP-9 as a potential biomarker for cancer invasion and metastasis. Anticancer Res 34:1355–1366Google Scholar
- Miller BW, Morton JP, Pinese M, Saturno G, Jamieson NB, Mcghee E, Timpson P, Leach J, Mcgarry L, Shanks E, Bailey P, Chang D, Oien K, Karim S, Au A, Steele C, Carter CR, Mckay C, Anderson K, Evans TRJ, Marais R, Springer C, Biankin A, Erler JT, Sansom OJ (2015) Targeting the LOX/hypoxia axis reverses many of the features that make pancreatic cancer deadly: inhibition of LOX abrogates metastasis and enhances drug efficacy. Embo Mol Med 7:1063–1076CrossRefGoogle Scholar
- Nagaharu K, Zhang XH, Yoshida T, Katoh D, Hanamura N, Kozuka Y, Ogawa T, Shiraishi T, Imanaka-Yoshida K (2011) Tenascin C induces epithelial-mesenchymal transition-like change accompanied by SRC activation and focal adhesion kinase phosphorylation in human breast cancer cells. Am J Pathol 178:754–763CrossRefGoogle Scholar
- Ozdemir BC, Pentcheva-Hoang T, Carstens JL, Zheng XF, Wu CC, Simpson TR, Laklai H, Sugimoto H, Kahlert C, Novitskiy SV, De Jesus-Acosta A, Sharma P, Heidari P, Mahmood U, Chin L, Moses HL, Weaver VM, Maitra A, Allison JP, Lebleu VS, Kalluri R (2014) Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival. Cancer Cell 25:719–734CrossRefGoogle Scholar
- Rhim AD, Oberstein PE, Thomas DH, Mirek ET, Palermo CF, Sastra SA, Dekleva EN, Saunders T, Becerra CP, Tattersa IW, Westphalen CB, Kitajewski J, Fernandez-Barrena MG, Fernandez-Zapico ME, Iacobuzio-Donahue C, Olive KP, Stanger BZ (2014) Stromal elements act to restrain, rather than support, pancreatic ductal adenocarcinoma. Cancer Cell 25:735–747CrossRefGoogle Scholar
- Rupp T, Langlois B, Koczorowska MM, Radwanska A, Sun Z, Hussenet T, Lefebvre O, Murdamoothoo D, Arnold C, Klein A, Biniossek ML, Hyenne V, Naudin E, Velazquez-Quesada I, Schilling O, Van Obberghen-Schilling E, Orend G (2016) Tenascin-C orchestrates glioblastoma angiogenesis by modulation of pro- and anti-angiogenic signaling. Cell Rep 17:2607–2619CrossRefGoogle Scholar
- Sanz-Moreno V, Gaggioli C, Yeo M, Albrengues J, Wallberg F, Viros A, Hooper S, Mitter R, Feral CC, Cook M, Larkin J, Marais R, Meneguzzi G, Sahai E, Marshall CJ (2011) ROCK and JAK1 signaling cooperate to control actomyosin contractility in tumor cells and stroma. Cancer Cell 20:229–245CrossRefGoogle Scholar