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

Caitlin O. McAtee, Christine Booth, Christian Elowsky, Lei Zhao, Jeremy Payne, Teresa Fangman, Steven H Caplan, Michael D. Henry, Melanie A. Simpson

Research output: Contribution to journalArticle

6 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)165-179
Number of pages15
JournalMatrix Biology
Volume78-79
DOIs
StatePublished - May 2019

Fingerprint

Exosomes
Hyaluronoglucosaminidase
Stromal Cells
Integrins
Cell Movement
Prostate
Neoplasms
Prostatic Neoplasms
Collagen Type IV
Tumor Cell Line
Cell Communication
Culture Media
Fibroblasts
Phosphorylation
Neoplasm Metastasis
Membranes

Keywords

  • Cell motility
  • Exosomes
  • Hyaluronan
  • Hyaluronidase
  • Prostate cancer
  • Stromal-epithelial crosstalk

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Prostate tumor cell exosomes containing hyaluronidase Hyal1 stimulate prostate stromal cell motility by engagement of FAK-mediated integrin signaling. / McAtee, Caitlin O.; Booth, Christine; Elowsky, Christian; Zhao, Lei; Payne, Jeremy; Fangman, Teresa; Caplan, Steven H; Henry, Michael D.; Simpson, Melanie A.

In: Matrix Biology, Vol. 78-79, 05.2019, p. 165-179.

Research output: Contribution to journalArticle

McAtee, Caitlin O. ; Booth, Christine ; Elowsky, Christian ; Zhao, Lei ; Payne, Jeremy ; Fangman, Teresa ; Caplan, Steven H ; Henry, Michael D. ; Simpson, Melanie A. / Prostate tumor cell exosomes containing hyaluronidase Hyal1 stimulate prostate stromal cell motility by engagement of FAK-mediated integrin signaling. In: Matrix Biology. 2019 ; Vol. 78-79. pp. 165-179.
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