成纤维细胞整合素α11β1是机械调节纤维粘连中的胶原组装受体。

IF 4.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Matrix Biology Pub Date : 2024-10-13 DOI:10.1016/j.matbio.2024.10.006

Moses Musiime , Pugazendhi Murugan Erusappan , Edna Cukierman , Joan Chang , Anders Molven , Uwe Hansen , Cédric Zeltz , Donald Gullberg

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引用次数: 0

摘要

有明显脱钙化的实体上皮癌的特点是胶原基质的过度沉积，这通常会支持肿瘤的进展。然而，胶原受体如何介导胶原纤维生成的机制仍大多不清楚。我们的研究表明，胶原结合整合素α11β1能与tensin-1共定位，并在人胰腺导管腺癌（PDAC）基质中沉积胶原蛋白I。除了人PDAC癌相关成纤维细胞（CAFs）表达的典型纤维粘附整合素α5β1外，tensin-1阳性纤维粘附还包含α11β1，但缺乏α1β1和α2β1。缺乏α5β1表达的CAF显示出机械调节的、依赖于tensin-1的α11β1纤维粘附，这表明这两种整合素在基于纤维粘附的新生纤维形成中发挥着独立的作用。此外，我们还证明细胞表面相关的胶原 I 组装需要α11β1，而不是α5β1的表达。总之，α11β1整合素是纤维粘连的一种新成分，在促纤维化条件下，它具有介导细胞表面新生胶原纤维形成的战略地位。

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Fibroblast integrin α11β1 is a collagen assembly receptor in mechanoregulated fibrillar adhesions

Solid epithelial cancers with significant desmoplasia are characterized by an excessive deposition of collagen-based matrix, which often supports tumor progression. However, the mechanism of how collagen receptors mediate collagen fibrillogenesis still remains mostly unclear.

We show that the collagen-binding integrin α11β1 can co-localize with tensin-1 and deposited collagen I in human pancreatic ductal adenocarcinoma (PDAC) stroma. In addition to the canonical fibrillar adhesion integrin α5β1 expressed by human PDAC cancer-associated fibroblasts (CAFs), tensin-1-positive fibrillar adhesions contained α11β1 but lacked α1β1 and α2β1. CAFs lacking α5β1 expression displayed mechanoregulated and tensin-1 dependent α11β1 fibrillar adhesions, suggesting independent roles of the two integrins with regards to fibrillar adhesions-based de novo fibrillogenesis. Further, we demonstrate that cell surface-associated collagen I assembly necessitated α11β1, but not α5β1 expression.

In summary, α11β1 integrin is a novel component of fibrillar adhesions, which is strategically positioned to mediate de novo collagen fibrillogenesis at the cell surface under pro-fibrotic conditions.

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来源期刊

Matrix Biology 生物-生化与分子生物学

CiteScore

11.40

自引率

4.30%

发文量

审稿时长

45 days

期刊介绍： Matrix Biology (established in 1980 as Collagen and Related Research) is a cutting-edge journal that is devoted to publishing the latest results in matrix biology research. We welcome articles that reside at the nexus of understanding the cellular and molecular pathophysiology of the extracellular matrix. Matrix Biology focusses on solving elusive questions, opening new avenues of thought and discovery, and challenging longstanding biological paradigms.