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Stroma cells: a novel target of herceptin activity
Chiara Corsini1, Patrizia Mancuso, Saki Paul
1Division of Hematology-Oncology, Department of Medicine, European Institute of Oncology, 20141 Milan, Italy.
Purpose:
Stroma cells play a relevant role in tumor development and progression. We investigated the activity of herceptin (HER), a humanized monoclonal antibody widely used for the treatment of HER2-overexpressing epithelial cancer, toward stroma cell lines L87/4 and L88/5.
Experimental Design:
We studied the antiproliferative potential of HER and role of human serum in HER activity. We also investigated the ability of HER to alter ancillary functions of L87/4 and L88/5, such as support to long-term hematopoiesis, growth factor production, breast cancer cell adhesion, and proliferation.
Results:
Flow cytometry showed that HER2 membrane expression in L87/4 and L88/5 stroma cells was intermediate between the expression in HER2-negative/dim MCF-7 breast cancer cells and HER2-bright SK-BC3 breast cancer cells. HER2 gene amplification was not detected by fluorescence in situ hybridization in either stromal cell lines. HER significantly inhibited L87/4 and L88/5 proliferation. Mean ID(50)s were found to be 2000 and 1700 micro g/ml for L87/4 and L88/5, respectively, after 3-day exposure and 800 micro g/ml for both cell lines after 9-day exposure. The presence of 10% human serum in the culture increased HER inhibitory activity. IC(50) of stroma cells was found to be intermediate between HER2-bright breast cancer cells (SK-BC3) and HER2-negative/dim breast cancer cells (MCF-7). The drug did not significantly affect the ability of stroma cells to support long-term hematopoiesis in the cobblestone area forming cell assay. In contrast, in coculture assay, MCF7 cells demonstrated a worse adhesion and growth capability on HER-treated stroma layers when compared with untreated stroma. Moreover, HER significantly reduced vascular endothelial growth factor production by L88/5 cells.
Conclusions:
Our data support the novel finding that HER may have a relevant activity against stroma cells.
Insights
Herceptin (HER) shows antiproliferative activity against cancer stroma cells. This study investigated HER
Area of Science:
- Oncology
- Cell Biology
- Pharmacology
Background:
- Stroma cells are crucial in tumor development and progression.
- Herceptin (HER) is a monoclonal antibody used to treat HER2-overexpressing epithelial cancers.
Purpose of the Study:
- To investigate the activity of Herceptin (HER) against cancer stroma cell lines L87/4 and L88/5.
- To assess the antiproliferative effects of HER on stroma cells and its impact on their supportive functions.
Main Methods:
- Assessed HER2 expression on stroma cells using flow cytometry.
- Studied the antiproliferative potential of HER on stroma cells in vitro.
- Evaluated HER's effect on stroma cell support for hematopoiesis, cancer cell adhesion, and growth factor production.
Main Results:
- HER significantly inhibited proliferation of stroma cell lines L87/4 and L88/5.
- HER reduced vascular endothelial growth factor production by L88/5 cells.
- HER-treated stroma layers impaired MCF7 breast cancer cell adhesion and growth.
Conclusions:
- Herceptin (HER) demonstrates significant antiproliferative activity against cancer stroma cells.
- HER may represent a novel therapeutic strategy targeting the tumor microenvironment.