Surface expression of Hsp25 and Hsp72 differentially regulates tumor growth and metastasis.
The expression of unique surface structures on tumors that allow for recognition and activation of host immunocompetent cells plays an important role in determining tumor growth and/or metastasis. Recent studies have identified an important role for heat shock proteins (Hsp) in antitumor surveillance; however, the exact role of Hsp expressed on the surface of tumors has not been fully addressed. In this study, we show that 4T1 mammary adenocarcinoma cells sorted for high Hsp25 surface expression (Hsp25(high)) grow significantly faster than cells sorted for intermediate Hsp25 surface expression (Hsp25(intermediate)) or wild-type 4T1 cells implanted into the abdominal breast gland of female BALB/c mice (p < 0.05). In addition, histological examination of lung tissues revealed that Hsp25(high) 4T1 cells metastasized to the lungs more aggressively than either Hsp25(intermediate) or wild-type 4T1 cells (p < 0.05). Exposure of 4T1 cells to nonlethal heat shock (43 degrees C, 30 min) induced the surface expression of Hsp72 and a concomitant reduction in Hsp25 surface expression. The growth and metastastic potential of Hsp72(+) 4T1 cells was significantly less than that of Hsp25(high), Hsp25(intermediate) or wild-type 4T1 cells (p < 0.05). Taken together, these studies identify an important role for expression of Hsp25 and Hsp72 during tumor growth and metastatic spread which might be helpful in the design of antimetastatic therapies.
Bausero
María A
MA
Center for Molecular Stress Response, Boston University Medical Center and Boston University School of Medicine, 650 Albany Street, Boston, MA 02118, USA.
Page
Diana T
DT
Osinaga
Eduardo
E
Asea
Alexzander
A
D000230:Adenocarcinoma / Q000556:secondary*; D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood*; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D055551:HSP27 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms / Q000503:physiopathology / Q000556:secondary*; D015674:Mammary Neoplasms, Animal / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018832:Molecular Chaperones; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000494:pharmacology; D009374:Neoplasms, Experimental; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D055551:HSP27 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins