title: Breast Cancer MDA-MB-231 Cells Use Secreted Heat Shock Protein-90alpha (Hsp90α) to Survive a Hostile Hypoxic Environment.
abstract: Rapidly growing tumours in vivo often outgrow their surrounding available blood supply, subjecting themselves to a severely hypoxic microenvironment. Understanding how tumour cells adapt themselves to survive hypoxia may help to develop new treatments of the tumours. Given the limited blood perfusion to the enlarging tumour, whatever factor(s) that allows the tumour cells to survive likely comes from the tumour cells themselves or its associated stromal cells. In this report, we show that HIF-1α-overexpressing breast cancer cells, MDA-MB-231, secrete heat shock protein-90alpha (Hsp90α) and use it to survive under hypoxia. Depletion of Hsp90α secretion from the tumour cells was permissive to cytotoxicity by hypoxia, whereas supplementation of Hsp90α-knockout tumour cells with recombinant Hsp90α, but not Hsp90β, protein prevented hypoxia-induced cell death via an autocrine mechanism through the LDL receptor-related protein-1 (LRP1) receptor. Finally, direct inhibition of the secreted Hsp90α with monoclonal antibody, 1G6-D7, enhanced tumour cell death under hypoxia. Therefore, secreted Hsp90α is a novel survival factor for certain tumours under hypoxia.
authors: Department of Dermatology and the Norris Comprehensive Cancer Centre, University of Southern California Keck Medical Centre,Los Angeles, CA 90033, USA.
authors: Hangming
authors: H
authors: Dong
authors: Department of Dermatology and the Norris Comprehensive Cancer Centre, University of Southern California Keck Medical Centre,Los Angeles, CA 90033, USA.
authors: Mengchen
authors: M
authors: Zou
authors: Department of Dermatology and the Norris Comprehensive Cancer Centre, University of Southern California Keck Medical Centre,Los Angeles, CA 90033, USA.
authors: Ayesha
authors: A
authors: Bhatia
authors: Department of Dermatology and the Norris Comprehensive Cancer Centre, University of Southern California Keck Medical Centre,Los Angeles, CA 90033, USA.
authors: Priyamvada
authors: P
authors: Jayaprakash
authors: Department of Pathology, University of Southern California Keck Medical Centre,Los Angeles, CA 90033, USA.
authors: Florence
authors: F
authors: Hofman
authors: Eli and Edythe Broad Centre for Regenerative Medicine and Stem Cell Research and Department of Cell &Neurobiology, University of Southern California Keck Medical Centre, Los Angeles, CA 90033, USA.
authors: Qilong
authors: Q
authors: Ying
authors: Department of Dermatology and the Norris Comprehensive Cancer Centre, University of Southern California Keck Medical Centre,Los Angeles, CA 90033, USA.
authors: Mei
authors: M
authors: Chen
authors: Department of Dermatology and the Norris Comprehensive Cancer Centre, University of Southern California Keck Medical Centre,Los Angeles, CA 90033, USA.
authors: David T
authors: DT
authors: Woodley
authors: Department of Dermatology and the Norris Comprehensive Cancer Centre, University of Southern California Keck Medical Centre,Los Angeles, CA 90033, USA.
authors: Wei
authors: W
authors: Li
mesh_terms: D019898:Autocrine Communication; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D055786:Gene Knockout Techniques; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D000072258:Tumor Hypoxia
chemical_list: C497442:HIF1A protein, human; D018841:HSP90 Heat-Shock Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit