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CD44 associates with EGFR and erbB2 in metastasizing mammary carcinoma cells
Manja Wobus1, Reshma Rangwala, Irena Sheyn
1Department of Cell Biology, Neurobiology & Anatomy, University of Cincinnati College of Medicine, Ohio 45267-0521, USA.
Abstract:
Type I receptor tyrosine kinases, including the epidermal growth factor receptor (EGFR) and erbB2, have been implicated in mammary carcinoma growth and metastasis. Recent evidence suggests that type I receptor signaling may be mediated by the CD44 family of transmembrane glycoproteins that also have been implicated in mammary tumor progression. Here, the authors tested whether CD44, EGFR, and erbB2 interacted and colocalized with one another in four mammary carcinoma cell lines (MCF-7, MDA-MB-231, MDA-MB-435, and MDA-MB-436) and in cytology samples obtained from patients with metastatic breast cancer. CD44 constitutively colocalized and coimmunoprecipitated with erbB2 and EGFR in all four mammary carcinoma cell lines. CD44 also colocalized with erbB2 and EGFR in all cytology samples expressing erbB2. CD44 colocalized with EGFR in cells from only 1 of 16 erbB2-negative cytology samples. These data indicate that CD44-EGFR-erbB2 protein complexes occur in a high proportion of metastatic mammary carcinomas and suggest that CD44-type I receptor colocalization may be a novel prognostic marker for aggressive mammary cancers.
Insights
CD44 protein complexes with EGFR and erbB2 in metastatic breast cancer cells. This CD44-EGFR-erbB2 colocalization may serve as a new prognostic marker for aggressive mammary tumors.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Type I receptor tyrosine kinases, such as epidermal growth factor receptor (EGFR) and erbB2, are involved in mammary carcinoma growth and metastasis.
- The CD44 family of transmembrane glycoproteins is also implicated in mammary tumor progression.
- Evidence suggests that type I receptor signaling might be mediated by CD44.
Purpose of the Study:
- To investigate the interaction and colocalization of CD44, EGFR, and erbB2.
- To determine if these protein complexes are present in mammary carcinoma cell lines and patient samples.
Main Methods:
- Analysis of four human mammary carcinoma cell lines (MCF-7, MDA-MB-231, MDA-MB-435, MDA-MB-436).
- Immunoprecipitation and colocalization studies using patient-derived cytology samples from metastatic breast cancer.
- Assessment of protein complex formation in both erbB2-positive and erbB2-negative samples.
Main Results:
- CD44 constitutively colocalized and coimmunoprecipitated with both erbB2 and EGFR in all tested mammary carcinoma cell lines.
- CD44 colocalization with erbB2 and EGFR was observed in all patient cytology samples that expressed erbB2.
- CD44 colocalized with EGFR in only one of sixteen erbB2-negative patient samples.
Conclusions:
- CD44-EGFR-erbB2 protein complexes are present in a significant proportion of metastatic mammary carcinomas.
- The colocalization of CD44 with type I receptors (EGFR and erbB2) may represent a novel prognostic marker for aggressive mammary cancers.
- These findings highlight a potential therapeutic target and diagnostic tool for advanced breast cancer.