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Colorectal Cancer Cell Surface Protein Profiling Using an Antibody Microarray and Fluorescence Multiplexing

Colorectal Cancer Cell Surface Protein Profiling Using an Antibody Microarray and Fluorescence Multiplexing

Published on: September 25, 2011

Colorectal cancer cells express functional cell surface-bound TGFbeta.

Kristi Baker¹, Pooja Raut, Jeremy R Jass

¹Department of Pathology, McGill University, Montréal, Québec, Canada. kristi.baker@mcgill.ca

International Journal of Cancer

|December 14, 2007

Summary

Cell surface-bound TGFbeta is expressed on colorectal cancer cells and plays a role in tumor cell interactions and immunosuppression. This finding offers new insights into cancer progression and potential therapeutic targets.

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Area of Science:

Oncology
Immunology
Cell Biology

Background:

Transforming Growth Factor beta (TGFbeta) signaling pathway disruptions are common in human adenocarcinomas.
TGFbeta influences cancer cell migration, metastasis, and tumor-mediated immunosuppression.
Membrane-bound TGFbeta is crucial for regulatory T cell suppressive function.

Purpose of the Study:

To investigate the expression and function of cell surface-bound TGFbeta on colorectal cancer cells.
To determine if this membrane-bound TGFbeta is signaling-competent and biologically active.

Main Methods:

Detection of cell surface-bound TGFbeta using antibodies specific for latent and mature forms.
Acid pulsing to assess the latent state of surface TGFbeta.
Coculture assays with cancer cells and CD8+ intraepithelial lymphocytes.
Assessment of TGFbeta activation and function in coculture.
Use of a furin inhibitor to evaluate its effect on membrane-bound TGFbeta expression.

Main Results:

Signaling-competent, endogenously derived cell surface-bound TGFbeta was detected on colorectal cancer cells.
Surface TGFbeta was detected by antibodies for both latent and mature forms, with increased detection after acid pulsing.
Cell-bound TGFbeta could be activated and utilized in a paracrine manner by other cancer cells and CD8+ lymphocytes.
A furin inhibitor reduced membranous TGFbeta expression on tumor cells.

Conclusions:

Signaling-competent membrane-bound TGFbeta on cancer cells is a key regulator of tumor cell interactions.
This mechanism likely influences interactions within the tumor microenvironment, including with immune cells.
The findings suggest a novel role for cell surface-bound TGFbeta in colorectal cancer progression and immunosuppression.