Publications

Publications

Integrin-Free Tetraspanin CD151 Can Inhibit Tumor Cell Motility upon Clustering and Is a Clinical Indicator of Prostate Cancer Progression

By:
Contributors: John D. Lewis Research Group

Cancer Res. 2014 Jan 1;74(1):173-87. doi: 10.1158/0008-5472.CAN-13-0275. Epub 2013 Nov 12.

Palmer TD1, Martínez CH, Vasquez C, Hebron KE, Jones-Paris C, Arnold SA, Chan SM, Chalasani V, Gomez-Lemus JA, Williams AK, Chin JL, Giannico GA, Ketova T, Lewis JD, Zijlstra A.

Abstract

Normal physiology relies on the organization of transmembrane proteins by molecular scaffolds, such as tetraspanins. Oncogenesis frequently involves changes in their organization or expression. The tetraspanin CD151 is thought to contribute to cancer progression through direct interaction with the laminin-binding integrins α3β1 and α6β1. However, this interaction cannot explain the ability of CD151 to control migration in the absence of these integrins or on non-laminin substrates. We demonstrate that CD151 can regulate tumor cell migration without direct integrin binding and that integrin-free CD151 (CD151(free)) correlates clinically with tumor progression and metastasis. Clustering CD151(free) through its integrin-binding domain promotes accumulation in areas of cell-cell contact, leading to enhanced adhesion and inhibition of tumor cell motility in vitro and in vivo. CD151(free) clustering is a strong regulator of motility even in the absence of α3 expression but requires PKCα, suggesting that CD151 can control migration independent of its integrin associations. The histologic detection of CD151(free) in prostate cancer correlates with poor patient outcome. When CD151(free) is present, patients are more likely to recur after radical prostatectomy and progression to metastatic disease is accelerated. Multivariable analysis identifies CD151(free) as an independent predictor of survival. Moreover, the detection of CD151(free) can stratify survival among patients with elevated prostate-specific antigen levels. Cumulatively, these studies demonstrate that a subpopulation of CD151 exists on the surface of tumor cells that can regulate migration independent of its integrin partner. The clinical correlation of CD151(free) with prostate cancer progression suggests that it may contribute to the disease and predict cancer progression.

PubMed

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Kaye Fund Awards: Congratulations to our APCaRI members!

University Hospital Foundation – Kaye Fund Awards

Congratulations to two APCaRI principal investigators; Dr. John Lewis and Dr. Frank Wuest for their 2018 Kaye Fund Awards! From an initial field of 80 applicants, 7 Kaye Fund Awards in total were given to medical researchers studying a diverse array of health-relevant topics of huge importance to Albertans and the rest of the world alike.

John Lewis’ project is titled “Improving the Management of Prostate Cancer Using Advanced Biofluid Diagnostics” and Frank Wuest’s project is “Novel Radiolabeled PSMA Inhibitors for Clinical PET Imaging of Prostate Cancer”. Both projects are poised to greatly improve prostate cancer diagnosis and treatment in the near future.

The University of Alberta Hospital (UAH), Kaye Edmonton Clinic (KEC) and the University Hospital Foundation (UHF) launched the Kaye Fund Competition in the fall of 2017. Recipients of this inaugural competition were announced July 4th, 2018. The Kaye Fund Competition aims to support individuals or collaborative, inter-disciplinary and multi-disciplinary teams in the pursuit of research, innovation and quality improvement projects that will establish new approaches to patient care.

The Kaye Fund Award is funded by a transformational $30 million donation from Mr. Donald Kaye. This gift is directed to advancing patient care and medical research to the Kaye Edmonton Clinic, and remains one of largest donations in the history of Canadian healthcare philanthropy.

Mr. Donald Kaye

Through his naming gift to the University Hospital Foundation, Donald Kaye has transformed years of hard work, prudent decision-making and wise investing into one of the largest donations in the history of Canadian healthcare philanthropy. And in doing so, Mr. Kaye is advancing patient care and medical research in a way that is both intently focused, and broadly based.  

 

 

- Perrin Beatty