Journal article
BST-2 promotes survival in circulation and pulmonary metastatic seeding of breast cancer cells
Scientific reports, Vol.8(1), pp.17608-14
12/04/2018
DOI: 10.1038/s41598-018-35710-y
PMCID: PMC6279795
PMID: 30514852
Abstract
Bone marrow stromal antigen 2 (BST-2) mediates various facets of cancer progression and metastasis. Here, we show that BST-2 is linked to poor survival in invasive breast cancer patients as its expression positively correlates with disease severity. However, the mechanisms that drive the pro-metastatic functions of BST-2 are not fully understood. Correlation of BST-2 expression and tumor aggressiveness was analyzed in human tissue samples. Migration, invasion, and competitive experimental metastasis assays were used to measure the cellular responses after silencing BST-2 expression. Using a mouse model of breast cancer, we show that BST-2 promotes metastasis independent of the primary tumor. Additional experiments show that suppression of BST-2 renders non-adherent cancer cells non-viable by sensitizing cells to anoikis. Embedment of cancer cells in basement membrane matrix reveals that silencing BTS-2 expression inhibits invadopodia formation, extracellular matrix degradation, and subsequent cell invasion. Competitive experimental pulmonary metastasis shows that silencing BST-2 reduces the numbers of viable circulating tumor cells (CTCs) and decreases the efficiency of lung colonization. Our data define a previously unknown function for BST-2 in the i) formation of invadopodia, ii) degradation of extracellular matrix, and iii) protection of CTCs from hemodynamic stress. We believe that physical (tractional forces) and biochemical (ECM type/composition) cues may control BST-2's role in cell survival and invadopodia formation. Collectively, our findings highlight BST-2 as a key factor that allows cancer cells to invade, survive in circulation, and at the metastatic site.
Details
- Title: Subtitle
- BST-2 promotes survival in circulation and pulmonary metastatic seeding of breast cancer cells
- Creators
- Wadie D Mahauad-Fernandez - Stanford University School of MedicineWasifa Naushad - University of the SciencesTyler D Panzner - Stony Brook UniversityAmani Bashir - University of Iowa Hospitals and ClinicsGeeta Lal - University of IowaChioma M Okeoma - Stony Brook University
- Resource Type
- Journal article
- Publication Details
- Scientific reports, Vol.8(1), pp.17608-14
- DOI
- 10.1038/s41598-018-35710-y
- PMID
- 30514852
- PMCID
- PMC6279795
- NLM abbreviation
- Sci Rep
- ISSN
- 2045-2322
- eISSN
- 2045-2322
- Language
- English
- Date published
- 12/04/2018
- Academic Unit
- Microbiology and Immunology; Stead Family Department of Pediatrics; Pathology; Surgery
- Record Identifier
- 9984185281202771
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