Stromal cell expression of caveolin-1 predicts outcome in breast cancer.
Caveolin-1 has been linked to tumor progression and clinical outcome in breast cancer, but a clear resolution of its role as a prognostic marker is lacking. We assessed caveolin-1 levels in normal breast tissue and two breast cancer cohorts for which outcome data were available. We found that caveolin-1 was not expressed in normal breast luminal epithelium but was present in the epithelial compartment of some tumors. We found no association between caveolin-1 expression in the epithelial compartment and clinical outcome. However, high levels of caveolin-1 in the stromal tissue surrounding the tumor, rather than within tumor cells, associated strongly with reduced metastasis and improved survival (P < 0.0001). The onset of mammary tumors driven by Her2/neu overexpression was accelerated in mice lacking caveolin-1, thereby supporting the observation that the presence of caveolin-1 in the tumor microenvironment modulates tumor development. These studies suggest that stromal caveolin-1 expression may be a potential therapeutic target and a valuable prognostic indicator of breast cancer progression.
Sloan
Erica K
EK
Peter MacCallum Cancer Centre, Locked Bag #1, A'Beckett St., Melbourne, Victoria, Australia, 8006.
Ciocca
Daniel R
DR
Pouliot
Normand
N
Natoli
Anthony
A
Restall
Christina
C
Henderson
Michael A
MA
Fanelli
Mariel A
MA
Cuello-Carrión
Fernando D
FD
Gago
Francisco E
FE
Anderson
Robin L
RL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051242:Caveolin 1 / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000096:biosynthesis; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism*; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D051242:Caveolin 1; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D011991:Receptors, Virus; C111417:Fam89b protein, mouse