Deletion of Col15a1 Modulates the Tumour Extracellular Matrix and Leads to Increased Tumour Growth in the MMTV-PyMT Mouse Mammary Carcinoma Model

Abstract

Basement membrane (BM) zone-associated collagen XV (ColXV) has been shown to suppress the malignancy of tumour cells, and its restin domain can inhibit angiogenesis. In human breast cancer, as well as in many other human carcinomas, ColXV is lost from the epithelial BM zone prior to tumour invasion. Here, we addressed the roles of ColXV in breast carcinogenesis using the transgenic MMTV-PyMT mouse mammary carcinoma model. We show here for the first time that the inactivation of Col15a1 in mice leads to changes in the fibrillar tumour matrix and to increased mammary tumour growth. ColXV is expressed by myoepithelial and endothelial cells in mammary tumours and is lost from the ductal BM along with the loss of the myoepithelial layer during cancer progression while persisting in blood vessels and capillaries, even in invasive tumours. However, despite the absence of anti-angiogenic restin domain, neovascularisation was reduced rather than increased in the ColXV-deficient mammary tumours compared to controls. We also show that, in robust tumour cell transplantation models or in a chemical-induced fibrosarcoma model, the inactivation of Col15a1 does not affect tumour growth or angiogenesis. In conclusion, our results support the proposed tumour suppressor function of ColXV in mammary carcinogenesis and reveal diverse roles of this collagen in different cancer types.

Assessment of circulating proteins in thyroid cancer: Proteome-wide Mendelian randomization and colocalization analysis

“…Collagens like COL15A1 and COL18A1 are integral to tissue structure. Their upregulation in TC may reflect altered extracellular matrix remodeling, a key factor in cancer invasion 39 Specifically, COL15A1, non-fibrillar collagen associated with basement membranes, has been found to be involved in smooth muscle cell proliferation and atherosclerosis. 40 Similarly, COL18A1, another non-fibrillar collagen, has been associated with various BPs, including angiogenesis and tumorigenesis.…”

A 20-Gene Signature Predicting Survival in Patients with Clear Cell Renal Cell Carcinoma Based on Basement Membrane

“…Moreover, the depletion of VCAN also markedly reduced the invasion and migration of cells, which was correlated with MMP7 reduction [ 25 ]. It has been reported that deletion of COL15A1 modulates the tumor ECM and leads to increased tumor growth in the mouse mammary carcinoma model [ 29 ]. The transcript levels of COL4A4 and 6 could act as potential indicators for early disease progression in ccRCC [ 30 ].…”

Upregulated integrin α11 in the stroma of cutaneous squamous cell carcinoma promotes skin carcinogenesis

“…To analyze the content of fibrillar collagen in skin tumors, Masson trichrome and picrosirius red stainings were performed as described previously ( 29 ). PFA-fixed tumor sections were dewaxed in xylene; rehydrated with decreasing ethanol series; and treated with a nuclear stain (Celestine blue and Harris’ hematoxylin), acid fuchsin, phosphomolybdic acid, and methyl blue stain (all reagents from Sigma–Aldrich).…”