Breast cancer metastatic potential: correlation with increased heterotypic gap junctional intercellular communication between breast cancer cells and osteoblastic cells.
The breast cancer metastasis-suppressor gene BRMS1 is downregulated in metastatic breast cancer cells. Previous reports have shown restoration of gap junctional intercellular communication (GJIC) in the metastatic human breast carcinoma cell line MDA-MB-435 (435) transfected with BRMS1 cDNA. Metastasis, to a large extent in most breast cancers, occurs to bone. However, the reason for this preferential metastasis is not known. We explored cell-to-cell communication between 435 carcinoma cells and a human osteoblastic cell line, hFOB1.19, to determine whether carcinoma cells can form gap junctions with bone cells and to explore the role of these heterotypic gap junctions and the BRMS1 gene in breast cancer metastasis to bone. 435 cells displayed greater cell-to-cell communication with hFOB 1.19 cells than with themselves. Transfection of BRMS1 into 435 cells increased homotypic gap junctional communication but did not significantly affect heterotypic communication with hFOBs. However, heterotypic communication of BRMS1 transfectants with hFOB cells was reduced relative to homotypic communication. In contrast, parental 435 cells displayed greater heterotypic communication with hFOBs relative to homotypic communication. Our results suggest that there are differences in the relative homotypic and heterotypic GJIC of metastasis-capable and -suppressed cell lines.
Kapoor
Preeti
P
Department of Orthopedics and Rehabilitation, Musculoskeletal Research Laboratory, Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, PA 17033, USA.
Saunders
Marnie M
MM
Li
Zhongyong
Z
Zhou
Zhiyi
Z
Sheaffer
Nate
N
Kunze
Elaine L
EL
Samant
Rajeev S
RS
Welch
Danny R
DR
Donahue
Henry J
HJ
D001859:Bone Neoplasms / Q000503:physiopathology* / Q000556:secondary*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D015820:Cadherins / Q000494:pharmacology; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology*; D002448:Cell Adhesion; D002450:Cell Communication; D002460:Cell Line; D017630:Connexins / Q000494:pharmacology; D015536:Down-Regulation; D005260:Female; D017629:Gap Junctions / Q000502:physiology*; D006801:Humans; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D009363:Neoplasm Proteins / Q000235:genetics* / Q000494:pharmacology*; D010006:Osteoblasts / Q000502:physiology*; D010641:Phenotype; D011379:Prognosis; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014407:Tumor Cells, Cultured
C410024:BRMS1 protein, human; D015820:Cadherins; D017630:Connexins; D009363:Neoplasm Proteins; D012097:Repressor Proteins