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αB-crystallin: a novel regulator of breast cancer metastasis to the brain.

Publication ,  Journal Article
Malin, D; Strekalova, E; Petrovic, V; Deal, AM; Al Ahmad, A; Adamo, B; Miller, CR; Ugolkov, A; Livasy, C; Fritchie, K; Hamilton, E; Geradts, J ...
Published in: Clin Cancer Res
January 1, 2014

PURPOSE: Basal-like breast tumors are typically (ER/PR/HER2) triple-negative and are associated with a high incidence of brain metastases and poor clinical outcomes. The molecular chaperone αB-crystallin is predominantly expressed in triple-negative breast cancer (TNBC) and contributes to an aggressive tumor phenotype in preclinical models. We investigated the potential role of αB-crystallin in brain metastasis in TNBCs. EXPERIMENTAL DESIGN: αB-crystallin expression in primary breast carcinomas and brain metastases was analyzed by immunohistochemistry among patients with breast cancer with brain metastases. αB-crystallin was overexpressed or silenced in two different TNBC cell lines. The effects on cell adhesion to human brain microvascular endothelial cells (HBMEC) or extracellular matrix proteins, transendothelial migration, and transmigration across a HBMEC/astrocyte coculture blood-brain barrier (BBB) model were examined. In addition, the effects of overexpressing or silencing αB-crystallin on brain metastasis in vivo were investigated using orthotopic TNBC models. RESULTS: In a cohort of women with breast cancer brain metastasis, αB-crystallin expression in primary breast carcinomas was associated with poor overall survival and poor survival after brain metastasis, even among patients with TNBC. Stable overexpression of αB-crystallin in TNBC cells enhanced adhesion to HBMECs, transendothelial migration, and BBB transmigration in vitro, whereas silencing αB-crystallin inhibited these events. αB-crystallin promoted adhesion of TNBC cells to HBMECs, at least in part, through an α3β1 integrin-dependent mechanism. αB-crystallin overexpression promoted brain metastasis, whereas silencing αB-crystallin inhibited brain metastasis in orthotopic TNBC models. CONCLUSION: αB-crystallin is a novel regulator of brain metastasis in TNBC and represents a potential biomarker and drug target for this aggressive disease.

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Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

January 1, 2014

Volume

20

Issue

1

Start / End Page

56 / 67

Location

United States

Related Subject Headings

  • alpha-Crystallin B Chain
  • Triple Negative Breast Neoplasms
  • Transendothelial and Transepithelial Migration
  • Oncology & Carcinogenesis
  • Neoplasm Transplantation
  • Mice, SCID
  • Mice, Knockout
  • Mice, Inbred NOD
  • Kaplan-Meier Estimate
  • Humans
 

Citation

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Chicago
ICMJE
MLA
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Malin, D., Strekalova, E., Petrovic, V., Deal, A. M., Al Ahmad, A., Adamo, B., … Cryns, V. L. (2014). αB-crystallin: a novel regulator of breast cancer metastasis to the brain. Clin Cancer Res, 20(1), 56–67. https://doi.org/10.1158/1078-0432.CCR-13-1255
Malin, Dmitry, Elena Strekalova, Vladimir Petrovic, Allison M. Deal, Abraham Al Ahmad, Barbara Adamo, C Ryan Miller, et al. “αB-crystallin: a novel regulator of breast cancer metastasis to the brain.Clin Cancer Res 20, no. 1 (January 1, 2014): 56–67. https://doi.org/10.1158/1078-0432.CCR-13-1255.
Malin D, Strekalova E, Petrovic V, Deal AM, Al Ahmad A, Adamo B, et al. αB-crystallin: a novel regulator of breast cancer metastasis to the brain. Clin Cancer Res. 2014 Jan 1;20(1):56–67.
Malin, Dmitry, et al. “αB-crystallin: a novel regulator of breast cancer metastasis to the brain.Clin Cancer Res, vol. 20, no. 1, Jan. 2014, pp. 56–67. Pubmed, doi:10.1158/1078-0432.CCR-13-1255.
Malin D, Strekalova E, Petrovic V, Deal AM, Al Ahmad A, Adamo B, Miller CR, Ugolkov A, Livasy C, Fritchie K, Hamilton E, Blackwell K, Geradts J, Ewend M, Carey L, Shusta EV, Anders CK, Cryns VL. αB-crystallin: a novel regulator of breast cancer metastasis to the brain. Clin Cancer Res. 2014 Jan 1;20(1):56–67.

Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

January 1, 2014

Volume

20

Issue

1

Start / End Page

56 / 67

Location

United States

Related Subject Headings

  • alpha-Crystallin B Chain
  • Triple Negative Breast Neoplasms
  • Transendothelial and Transepithelial Migration
  • Oncology & Carcinogenesis
  • Neoplasm Transplantation
  • Mice, SCID
  • Mice, Knockout
  • Mice, Inbred NOD
  • Kaplan-Meier Estimate
  • Humans