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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It’s Movember, time to Grow a Mo for a Bro!

It’s Movember, time to grow your moustache to raise funds and awareness of some serious health risks that men face, like suicide, testicular cancer and prostate cancer. Maybe growing a moustache isn’t your thing? No problem, host a Mo-ment for the men in your life instead!

APCaRI is a key stakeholder in the TrueNTH Global Registry; contributing 92% of the submitted patients in February 2018. Recently described by Evans et al., 2017 in an article published in BMJ Open, this project was established as an international registry with the goal to monitor the care of men with localised prostate cancer from 13 Movember-fundraising countries. Prostate cancer treatment and outcomes for men vary according to where they live, their race and the care they receive. The TrueNTH Global Registry is collecting a dataset based on the International Consortium for Health Outcome Measures (ICHOM) so we can better understand how to improve the care and treatment of men with localized prostate cancer, regardless of ethnicity and geography.

Please check out previous APCaRI blog posts that have talked about Movember (@Movember); the international Mens’ health Awareness charity, and about TrueNTH (@TrueNTH_Canada); a program funded by Prostate Cancer Canada (PCC) and the Movember Foundation that aims to improve the quality of life of men with prostate cancer and their families.

So start growing (or attach) your moustache today to raise funds and awareness to improve mens’ health!

- Perrin Beatty