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CCR5 antagonist blocks metastasis of basal breast cancer cells

Marco Velasco-Velázquez1, Xuanmao Jiao, Marisol De La Fuente

  • 1Kimmel Cancer Center, Department of Cancer Biology and Stem Cell Biology and Regenerative Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA. marcovelasco@unam.mx

Cancer Research
|May 29, 2012
PubMed

Insights

Chemokine CCL5 and its receptor CCR5 are upregulated in basal and HER-2 breast cancers. CCR5 antagonists reduced invasion and metastasis, suggesting potential adjuvant therapy for basal subtype breast cancer.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • The roles of chemokine C-C motif ligand 5 (CCL5) and its receptor C-C motif chemokine receptor 5 (CCR5) in breast cancer progression are not fully understood.
  • Previous research has not definitively established the involvement of CCL5/CCR5 in specific breast cancer subtypes or their contribution to metastasis.

Purpose of the Study:

  • To investigate the expression and functional role of CCL5 and CCR5 in human breast cancer.
  • To evaluate the therapeutic potential of CCR5 antagonists in reducing breast cancer cell invasion and metastasis.

Main Methods:

  • Microarray analysis of 2,254 human breast cancer specimens to assess CCL5 and CCR5 expression.
  • Functional assays using breast cancer cell lines to determine CCR5 response to CCL5 and the effect of CCR5 antagonists (maraviroc, vicriviroc).
  • Preclinical mouse model to evaluate the efficacy of maraviroc in reducing pulmonary metastasis.

Main Results:

  • Increased expression of CCL5 and CCR5 was observed in basal and HER-2 genetic subtypes of breast cancer.
  • Breast cancer cells expressing CCR5 showed a functional response to CCL5, and oncogene transformation induced CCR5 expression.
  • Cells with functional CCR5 exhibited increased invasiveness; CCR5 antagonists reduced in vitro invasion and in vivo pulmonary metastasis in a preclinical model.
  • CCR5 antagonists did not affect breast cancer cell proliferation or viability.

Conclusions:

  • CCL5/CCR5 signaling plays a critical role in the invasiveness of basal breast cancer cells.
  • CCR5 antagonists demonstrate potential as an adjuvant therapy to mitigate metastasis risk in patients with the basal breast cancer subtype.

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