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Three Dimensional Cultures: A Tool To Study Normal Acinar Architecture vs. Malignant Transformation Of Breast Cells
Published on: April 25, 2014
CD151 accelerates breast cancer by regulating alpha 6 integrin function, signaling, and molecular organization
Xiuwei H Yang1, Andrea L Richardson, Maria I Torres-Arzayus
1Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Cancer Research
|May 3, 2008
Summary
CD151 protein, a regulator of integrins, is elevated in aggressive breast cancers. Its removal inhibited tumor cell invasion and progression, suggesting CD151 as a potential therapeutic target.
Area of Science:
- Cell Biology
- Molecular Oncology
- Cancer Research
Background:
- CD151 protein regulates laminin-binding integrins, forming tetraspanin-enriched microdomains.
- CD151 expression is elevated in 31% of human breast cancers, particularly high-grade and triple-negative subtypes.
Purpose of the Study:
- To investigate the functional role of CD151-integrin complexes in basal-like mammary tumor progression.
- To evaluate CD151 as a potential therapeutic target in breast cancer.
Main Methods:
- CD151 ablation in basal-like mammary tumor cells.
- Assessment of cell migration, invasion, spreading, and signaling pathways (FAK, Rac1, lck).
- Analysis of epidermal growth factor receptor (EGFR)-alpha(6) integrin collaboration and integrin subcellular localization.
- Xenograft models (ectopic and orthotopic) to assess tumor progression.
Main Results:
- CD151 ablation significantly reduced mammary cell migration, invasion, and spreading.
- Disruption of EGFR-alpha(6) integrin collaboration and altered alpha(6)beta(4) integrin localization were observed.
- CD151 ablation delayed tumor progression in preclinical models.
- CD151 links alpha(6) integrins within tetraspanin-enriched microdomains, crucial for tumor cell functions.
Conclusions:
- CD151-alpha(6) integrin complexes are functionally important in basal-like mammary tumor progression.
- Alpha(6) integrins mediate their function through CD151 linkage within tetraspanin-enriched microdomains.
- CD151 represents a promising therapeutic target with potential selectivity for cancer cells over normal tissues.
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