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Collagen Type XI Inhibits Lung Cancer-Associated Fibroblast Functions and Restrains the Integrin Binding Site Availability on Collagen Type I Matrix.
Zeltz, Cédric; Khalil, Maryam; Navab, Roya; Tsao, Ming-Sound.
Afiliación
  • Zeltz C; Princess Margaret Cancer Center, University Health Network, Toronto, ON M5G 1L7, Canada.
  • Khalil M; Princess Margaret Cancer Center, University Health Network, Toronto, ON M5G 1L7, Canada.
  • Navab R; Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
  • Tsao MS; Princess Margaret Cancer Center, University Health Network, Toronto, ON M5G 1L7, Canada.
Int J Mol Sci ; 23(19)2022 Oct 03.
Article en En | MEDLINE | ID: mdl-36233024
The tumor microenvironment, including cancer-associated fibroblast (CAF), plays an active role in non-small cell lung cancer (NSCLC) development and progression. We previously reported that collagen type XI and integrin α11, a collagen receptor, were upregulated in NSCLC; the latter promotes tumor growth and metastasis. We here explored the role of collagen type XI in NSCLC stroma. We showed that the presence of collagen type XI in collagen type I matrices inhibits CAF-mediated collagen remodeling and cell migration. This resulted in the inhibition of CAF-dependent lung-tumor cell invasion. Among the collagen receptors expressed on CAF, we determined that DDR2 and integrin α2ß1, but not integrin α11ß1, mediated the high-affinity binding to collagen type XI. We further demonstrated that collagen type XI restrained the integrin binding site availability on collagen type I matrices, thus limiting cell interaction with collagen type I. As a consequence, CAFs failed to activate FAK, p38 and Akt one hour after they interacted with collagen type I/XI. We concluded that collagen type XI may have a competitive negative feedback role on the binding of collagen type I to its receptors.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma de Pulmón de Células no Pequeñas / Fibroblastos Asociados al Cáncer / Neoplasias Pulmonares Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Revista: Int J Mol Sci Año: 2022 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma de Pulmón de Células no Pequeñas / Fibroblastos Asociados al Cáncer / Neoplasias Pulmonares Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Revista: Int J Mol Sci Año: 2022 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Suiza