Effects of extracellular matrix components and dihydrotestosterone on the structure and function of human prostate cancer cells.
The extracellular matrix (ECM) has been shown to play a major role in cell structure and function. Several studies have demonstrated that the ECM can alter cell morphology and effect DNA synthesis and gene expression. The ECM also interacts with growth hormones which have been shown to be located in or near the ECM where they are believed to effect cell structure and function. In the nontransformed cell, these ECM and hormone-mediated effects appear to be tightly regulated and this is believed to be accomplished through cell receptor-tissue matrix interactions. We, therefore, undertook a study to determine the effects of a variety of ECM components and the adrogenic hormone dihydrotestosterone (DHT) on the structure and function of the human prostate cancer cell line, LNCaP. The effects of individual matrix components in the presence and absence of 1 nM DHT on the static and dynamic morphology, growth rate, and PSA production of the LNCaP cell line were studied. We determine that the ECM and DHT interact in complex ways to effect cell structure and function. DHT produced alterations in cytoplasmic structure that increased cell size and decreased the nuclear area/cytoplasmic area ratio. Dynamic cell structure as measured by cell motility was very sensitive to the ECM components and the presence of DHT. PSA and growth could be regulated by substratum and DHT and there was an inverse relationship between PSA production and growth rate. These data exemplify the complex interactions which occur between prostate cancer cells, ECM components, and exogenous DHT that are reflected in cell structure and function.
Murphy
B C
BC
Johns Hopkins Oncology Center, Johns Hopkins School of Medicine, Baltimore, Maryland.
Pienta
K J
KJ
Coffey
D S
DS
D000951:Antigens, Neoplasm / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D002465:Cell Movement / Q000187:drug effects; D002467:Cell Nucleus / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology*; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004549:Elastin / Q000494:pharmacology*; D006801:Humans; D007797:Laminin / Q000494:pharmacology*; D008297:Male; D017430:Prostate-Specific Antigen; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D007797:Laminin; D013196:Dihydrotestosterone; D003094:Collagen; D004549:Elastin; D017430:Prostate-Specific Antigen