Prostate tumor cell exosomes containing hyaluronidase Hyal1 stimulate prostate stromal cell motility by engagement of FAK-mediated integrin signaling

Matrix Biology : Journal of the International Society for Matrix Biology
Caitlin O McAteeMelanie A Simpson

Abstract

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 throug...Continue Reading

Citations

Mar 31, 2019·Molecular Cancer·Miaowei WuXiao-Fang Yu
Nov 28, 2019·Cancer Metastasis Reviews·Alakesh DasIrit Sagi
Aug 5, 2020·Cell Communication and Signaling : CCS·Wei WangLi Qin
Sep 23, 2020·International Journal of Molecular Sciences·Issraa ShoucairCathie Garnis
Feb 11, 2020·Frontiers in Pharmacology·Nik Nur Syazana Binti Nik Mohamed Kamal, Wan Nazatul Shima Shahidan
Apr 4, 2021·International Journal of Molecular Sciences·Theresa Akoto, Sharanjot Saini
Apr 4, 2021·Cancers·Zoi PiperigkouNikos K Karamanos
Apr 11, 2021·Matrix Biology : Journal of the International Society for Matrix Biology·Thomas NeillRenato V Iozzo
May 22, 2021·Frontiers in Cell and Developmental Biology·Zhengfan GaoYong Li
Nov 14, 2021·Cell Communication and Signaling : CCS·Pia GiovannelliGabriella Castoria

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