2019 journal article
Prostate tumor cell exosomes containing hyaluronidase Hyal1 stimulate prostate stromal cell motility by engagement of FAK-mediated integrin signaling
MATRIX BIOLOGY, 78-79, 165–179.
author keywords: Hyaluronan; Hyaluronidase; Prostate cancer; Cell motility; Exosomes; Stromal-epithelial crosstalk
MeSH headings : Autophagosomes / metabolism; Cell Adhesion; Cell Communication; Cell Culture Techniques; Cell Line, Tumor; Cell Movement; Enzyme Activation; Exosomes / metabolism; Focal Adhesion Kinase 1 / metabolism; Gene Expression Regulation, Neoplastic; Humans; Hyaluronoglucosaminidase / metabolism; Integrins / metabolism; Male; Microtubule-Associated Proteins / metabolism; Prostatic Neoplasms / metabolism; Prostatic Neoplasms / pathology; Signal Transduction; Stromal Cells / cytology; Stromal Cells / metabolism; Stromal Cells / pathology; Up-Regulation
TL;DR:
The presence of Hyal1 in tumor-derived exosome and its ability to impact the behavior of stromal cells suggests cell-cell communication via exosomes is a novel mechanism by which elevated Hyal 1 promotes prostate cancer progression.
(via Semantic Scholar)
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science; OpenAlex)
Source: Web Of Science
Added: June 17, 2019
The hyaluronidase Hyal1 is clinically and functionally implicated in prostate cancer progression and metastasis. Elevated Hyal1 accelerates vesicular trafficking in prostate tumor cells, thereby enhancing their metastatic potential in an autocrine manner through increased motility and proliferation. In this report, we found Hyal1 protein is a component of exosomes produced by prostate tumor cell lines overexpressing Hyal1. We investigated the role of exosomally shed Hyal1 in modulating tumor cell autonomous functions and in modifying the behavior of prostate stromal cells. Catalytic activity of Hyal1 was necessary for enrichment of Hyal1 in the exosome fraction, which was associated with increased presence of LC3BII, an autophagic marker, in the exosomes. Hyal1-positive exosome contents were internalized from the culture medium by WPMY-1 prostate stromal fibroblasts. Treatment of prostate stromal cells with tumor exosomes did not affect proliferation, but robustly stimulated their migration in a manner dependent on Hyal1 catalytic activity. Increased motility of exosome-treated stromal cells was accompanied by enhanced adhesion to a type IV collagen matrix, as well as increased FAK phosphorylation and integrin engagement through dynamic membrane residence of β1 integrins. The presence of Hyal1 in tumor-derived exosomes and its ability to impact the behavior of stromal cells suggests cell-cell communication via exosomes is a novel mechanism by which elevated Hyal1 promotes prostate cancer progression.