RESUMO
The expression in vivo of FMS transcripts and antigen by neoplastic epithelial cells was demonstrated immunohistochemically or by in situ hybridization in sixteen of seventeen human breast carcinoma specimens and one case of sclerosing adenosis. Expression of CSF-1 receptor (FMS) transcripts and protein was also observed in vitro in two or three breast carcinoma-derived cell lines and was dramatically increased by dexamethasone, a potent glucocorticoid and inducer of mammary epithelial cell differentiation. Immunohistochemical staining with an anti-CSF-1 antibody identified neoplastic epithelial cell co-expression of fms and CSF-1 antigens in more than one-third of the fms-positive invasive carcinoma specimens. These results suggest that autocrine and paracrine interactions of the lymphohematopoietic cytokine CSF-1 and its receptor may participate in the biology of human mammary neoplasms.
Assuntos
Neoplasias da Mama/metabolismo , Fatores Estimuladores de Colônias/metabolismo , Receptor de Fator Estimulador de Colônias de Macrófagos/metabolismo , Receptores de Fator Estimulador de Colônias/metabolismo , Transcrição Gênica/genética , Northern Blotting , Neoplasias da Mama/patologia , Neoplasias da Mama/ultraestrutura , Linhagem Celular , Fatores Estimuladores de Colônias/genética , DNA de Neoplasias/genética , DNA de Neoplasias/metabolismo , DNA de Neoplasias/ultraestrutura , Dexametasona/farmacologia , Amplificação de Genes , Expressão Gênica/fisiologia , Humanos , Imuno-Histoquímica , Hibridização de Ácido Nucleico , Reação em Cadeia da Polimerase , Receptor de Fator Estimulador de Colônias de Macrófagos/genética , Receptores de Fator Estimulador de Colônias/fisiologia , Transcrição Gênica/efeitos dos fármacosRESUMO
Endometrial epithelial cell expression of CSF-1 and FMS antigens was studied in vivo and in vitro in 24 human endometrial carcinoma and 11 benign endometrial biopsy specimens. Twenty-one of 24 adenocarcinomas and 4 of 11 benign lesions stained positively (by IHC) with rabbit anti-human CSF-1 antibodies, while all 24 carcinomas and 3 out of 11 benign lesions (all secretory endometrial specimens) showed significant IHC staining (1+ or greater) of epithelial elements and tissue macrophages with a mouse anti-FMS (CSF-1 receptor) monoclonal antibody. CSF-1 levels in plasma from endometrial carcinoma patients (85 samples, 24 patients) were also found to be markedly elevated (some greater than 100 ng/ml) in patients with active or recurrent disease. In vitro, several endometrial carcinoma cell lines were shown to express FMS complementary transcripts and FMS antigen which were very similar if not identical to those expressed in choriocarcinoma cell line positive controls. Autocrine and paracrine effects mediated by tumor or stromally produced CSF-1 and a tumor epithelial cell CSF-1 receptor may therefore contribute to the biological behavior of endometrial neoplasms in vivo and in vitro.
