Peer Reviewed

1

Document Type

Article

Publication Date

10-5-2015

Keywords

Animals, Antigens, CD44, Bone Neoplasms, Breast Neoplasms, Cell Adhesion, Cell Line, Tumor, Cell Movement, Cell Survival, Disease-Free Survival, Female, Gene Knockdown Techniques, Humans, Kaplan-Meier Estimate, Lymphatic Metastasis, Mice, Nude, Middle Aged, Neoplasm Grading, Phenotype, Proportional Hazards Models, RNA Interference, Risk Factors, Signal Transduction, Time Factors, Transfection, Tumor Burden

Comments

The original article is available at http://www.impactjournals.com

Abstract

Metastasis is the predominant cause of death from cancer yet we have few biomarkers to predict patients at increased risk of metastasis and are unable to effectively treat disseminated disease. Analysis of 448 primary breast tumors determined that expression of the hylauronan receptor CD44 associated with high grade (p = 0.046), ER- (p = 0.001) and PR-negative tumors (p = 0.029), and correlated with increased distant recurrence and reduced disease-free survival in patients with lymph-node positive or large tumors. To determine its functional role in distant metastasis, CD44 was knocked-down in MDA-MB-231 cells using two independent shRNA sequences. Loss of CD44 attenuated tumor cell adhesion to endothelial cells and reduced cell invasion but did not affect proliferation in vitro. To verify the importance of CD44 to post-intravasation events, tumor formation was assessed by quantitative in vivo imaging and post-mortem tissue analysis following an intra-cardiac injection of transfected cells. CD44 knock-down increased survival and decreased overall tumor burden at multiple sites, including the skeleton in vivo. We conclude that elevated CD44 expression on tumour cells within the systemic circulation increases the efficiency of post-intravasation events and distant metastasis in vivo, consistent with its association with increased distant recurrence and reduced disease-free survival in patients.

Disciplines

Medicine and Health Sciences | Surgery

Citation

McFarlane S, Coulter JA, Tibbits P, O'Grady A, McFarlane C, Montgomery N, Hill A, McCarthy HO, Young LS, Kay EW, Isacke CM, Waugh DJ. CD44 increases the efficiency of distant metastasis of breast cancer. Oncotarget. 2015;6(13):11465-76.

PubMed ID

25888636

DOI Link

10.18632/oncotarget.3410

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.

Included in

Surgery Commons

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