Uncovering mediators of collagen degradation in the tumor microenvironment

• DOI: 10.1016/j.mbplus.2022.100101
• Publication Date: 2022-01-28T06:01:25Z
• Authors: Marie-Louise Thor...; Marco Carretta; Christina Jensen; Kasper Mølgaard; Henrik J. Jürgensen; Lars H. Engelholm; Niels Behrendt; Nicholas Willumsen; Daniel H. Madsen
• Keywords: Internalization; Type I collagen; Cleavage (geology)

Increased remodeling of the extracellular matrix in malignant tumors has been shown to correlate with tumor aggressiveness and a poor prognosis. This involves degradation original (ECM) deposition new tumor-supporting ECM. The main constituent ECM is collagen turnover mainly occurs sequential manner, where initial proteolytic cleavage insoluble fibers followed by cellular internalization large well-defined fragments for lysosomal degradation. However, despite extensive research field, lack consensus on which cell types within microenvironment express involved proteases still exists. Furthermore, relative contribution different not well-established. Here, we developed quantitative ex vivo assays show that responsible two murine syngeneic models are metalloproteinases produced cancer-associated fibroblasts endocytosed primarily tumor-associated macrophages from stroma. Using mannose receptor-deficient mice, this receptor essential collagen-internalization macrophages. Together, these findings identify entire pathway, endocytosis intracellular