The extracellular matrix proteins type I collagen, type III collagen, fibronectin, and laminin 421 stimulate migration of cancer cells

Abstract

For metastasis formation, individual cells from a primary tumor must migrate toward other tissues. The aim of this study was to determine if mesenchymal stromal cells (MSCs) from human bone marrow are able to emit signals that induce this migratory activity in cancer cells. We separated the supernatant of MSCs derived from human bone marrow by size‐exclusion and ion‐exchange chromatography and have subsequently studied the migratory behavior of the prostate cancer cell line PC3 and the breast cancer cell line MDA‐MB‐231 toward the respective fractions in a transwell migration assay. We identified the extracellular matrix (ECM) proteins type I collagen, type III collagen, fibronectin, and laminin 421 as potential drivers of cancer cell migration. These results could be reproduced using the corresponding isolated or recombinant ECM proteins. Knockdown of the gene encoding beta 1 integrin, an important cell surface receptor for fibronectin, has led to inhibition of cancer cell migration. This supports the hypothesis that beta 1 integrin signaling represents an initial event that leads to metastasis, and that signaling is triggered by binding of integrin heterodimers to ECM molecules. Further characterization of signaling factors and their respective receptors will have implications for anticancer drug development.

Extracellular matrix mediates moruloid-blastuloid morphodynamics in malignant ovarian spheroids

“…The appearance of the BM results in loss in cell movement; compaction and stabilization of intercellular relationships and formation of lumen. In fact, down-regulation of fibronectin-1 in blastuloid spheroids, is consistent with its well-established role in driving migration of cancer cells (Graf et al, 2021). Moreover, fibronectin is a well-known mesenchymal marker, and its down-regulation in blastuloid spheroids, along with establishment of lumen, polarity, and a BM-like ECM coat implies a consonance between moruloid-to-blastuloid and mesenchymal to epithelial transition.…”

An avian embryo patient-derived xenograft model for preclinical studies of human breast cancers

“…Interestingly, several molecular signals reported to promote the establishment of metastatic foci in the bones are expressed during somitogenesis. This holds true for the chemokine CXCL12/SDF-1, WNTS, and HGF, as well as extracellular matrix proteins such as tenascins and fibronectins ( Clézardin et al., 2021 ; Graf et al., 2021 ; Kar et al., 2020 ; Previdi et al., 2010 ; Scaal et al., 1999 ; Stebler et al., 2004 ; Tomás et al., 2011 ).…”

“…Nevertheless, although immature, this somitic territory holds interesting molecular similarities with the bone tissue. Likewise, signaling reported for their instructive role during the bone metastatic process like CXCL12/SDF-1, WNT, and HGF, as well as extracellular matrix components like tenascin-C or fibronectins, are also present in the developing somitic domain ( Clézardin et al., 2021 ; Graf et al., 2021 ; Kar et al., 2020 ; Previdi et al., 2010 ; Scaal et al., 1999 ; Stebler et al., 2004 ; Tomás et al., 2011 ). This likely contributes to define the behaviors of grafted tumoral cells.…”

The role of network‐forming collagens in cancer progression

“…Typically, fibril‐forming collagens are characterized by a large extracellular fiber with a continuous triple helix structure of about 300 nm, and a large peptide chain as long as 1000 amino acids. Previous studies have demonstrated that fibril‐forming collagens, such as type I/III/XI collagens, can promote tumor progression and serve as prognostic markers 9‐12 …”