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Updated: Jul 9, 2026
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
Abstract:
Disruptions to the TGFbeta signaling pathway have been implicated in most human adenocarcinomas. In addition to its role in cancer cell migration and metastasis, TGFbeta has been implicated in tumor-mediated immunosuppression. Membrane-bound TGFbeta has previously been reported to be expressed on a subset of regulatory T cells and was shown to be critical to their immune suppressive function. In the present study, we document expression of a signaling competent, endogenously derived form of cell surface-bound TGFbeta on colorectal cancer cells. While antibodies against only the mature form of TGFbeta failed to label cells, surface-bound TGFbeta was clearly detected by antibodies specific for both the latent and mature forms of the cytokine. Confirming the notion that the surface TGFbeta was in latent form, brief acid pulsing of the cells increased the amount of detectable membrane-associated TGFbeta. In coculture assays, this cell-bound TGFbeta could be activated and utilized in a paracrine fashion both by other cancer cells and by CD8+ intraepithelial lymphocytes. This effect was abrogated by the use of a furin inhibitor which decreased the membranous expression of TGFbeta on the tumor cells. Signaling competent membrane-bound TGFbeta on cancer cells is thus likely to be a key player in regulating tumor cell interactions with each other as well as with other cells in their microenvironment.
Insights
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.
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.
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