Breast cancer micrometastases: different interactions of carcinoma cells with normal and cancer patients' bone marrow stromata.
The apparently dormant breast cancer micrometastases in haemopoietic marrow are correlated with distant metastatic carcinoma dissemination. We studied in vitro interactions of carcinoma cells with adjacent stromata, using connective tissue cell cultures from breast and bone marrow samples of normal donors, comparing them to the pericancerous breast tissue and bone marrows of 12 selected patients with invasive breast carcinomas. Cancer cells were detected by immunocytochemistry and RT-PCR in all the bone marrows and in most blood samples of the studied patients. We monitored the growth and interaction of carcinoma MCF-7 cells with the stromata. The normal breast stroma sustained typical massive cancer growth. The pericancerous breast stroma induced the invasive mesenchymal pattern of growth. Normal bone marrow stroma induced the same conversion and was highly adhesive, retaining the cells in the stroma, but carcinoma patients' bone marrow stromata underwent low adhesive interactions with cancer cells, releasing them potentially into the circulation. The semi-quantitative RT-PCR indicated an enhanced expression of the hepatocyte growth factor and its receptor c-met in breast and bone marrow stromata of cancer patients. The input of cancer cells into the normal bone marrow may induce modifications of the local microenvironment, favourable for growth and release of carcinoma cells into the systemic circulation, which correlate with the poor prognosis of patients with bone marrow micrometastases.
Nicola
Maria-Helena A
MH
Departamento de Histologia e Embriologia, Instituto de Ciências Biomédicas, and Programa Avançado de Biologia Celular Aplicada a Medicina, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Bizon
Rosana
R
Machado
Janaina J S
JJ
Sollero
Tereza
T
Rodarte
Renato S
RS
Nobre
João S
JS
Magalhães
Maurício M
MM
Takiya
Christina M
CM
Borojevic
Radovan
R
D001853:Bone Marrow / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion; D002455:Cell Division; D002460:Cell Line; D018920:Coculture Techniques; D018076:DNA, Complementary / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate / Q000494:pharmacology; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis; D006801:Humans; D007633:Keratins / Q000096:biosynthesis; D009362:Neoplasm Metastasis; D011485:Protein Binding; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis; D012313:RNA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D012313:RNA; D017228:Hepatocyte Growth Factor; D007633:Keratins; D019859:Proto-Oncogene Proteins c-met; D016650:Fluorescein-5-isothiocyanate