Phenotypic conversion of human mammary carcinoma cells by autocrine human growth hormone.
We report here that autocrine production of human growth hormone (hGH) results in a phenotypic conversion of mammary carcinoma cells such that they exhibit the morphological and molecular characteristics of a mesenchymal cell, including expression of fibronectin and vimentin. Autocrine production of hGH resulted in reduced plakoglobin expression and relocalization of E-cadherin to the cytoplasm, leading to dissolution of cell-cell contacts and decreased cell height. These phenotypic changes were accompanied by an increase in cell motility, elevated activity of specific matrix metalloproteinases, and an acquired ability to invade a reconstituted basement membrane. Forced expression of plakoglobin significantly decreased mammary carcinoma cell migration and invasion stimulated by autocrine hGH. In vivo, autocrine hGH stimulated local invasion of mammary carcinoma cells concomitant with a prominent stromal reaction in comparison with well delineated and capsulated growth of mammary carcinoma cells lacking autocrine production of hGH. Thus, autocrine production of hGH by mammary carcinoma cells is sufficient for generation of an invasive phenotype. Therapeutic targeting of autocrine hGH may provide a mechanistic approach to prevent metastatic extension of human mammary carcinoma.
Mukhina
Svetlana
S
Institute of Molecular and Cell Biology, 30 Medical Drive, Republic of Singapore 117609.
Mertani
Hichem C
HC
Guo
Ke
K
Lee
Kok-Onn
KO
Gluckman
Peter D
PD
Lobie
Peter E
PE
D019898:Autocrine Communication; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D019382:Human Growth Hormone / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008648:Mesoderm / Q000378:metabolism / Q000473:pathology; D009361:Neoplasm Invasiveness; D010641:Phenotype; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection
D004273:DNA, Neoplasm; D011994:Recombinant Proteins; D019382:Human Growth Hormone