Calcium signals in prostate cancer cells: specific activation by bone-matrix proteins.
Cancer of the prostate commonly metastasizes to bony sites where cells acquire an aggressive, rapidly proliferating, androgen-independent phenotype. The interaction between bone and prostate, thus, becomes a key factor in disease progression. Fluctuations in intracellular ionized Ca2+ [Ca2+]i are rapid, regulated signal transduction events often associated with cell proliferation. Hence, Ca2+ signals provide a convenient measure of early events in cancer cell growth. This study developed single cell fluorescent imaging techniques to visualize Ca2+ signals in Fura-2 loaded prostatic cancer cell lines of various metastatic phenotypes. Solubilized bone fractions containing extracellular matrix and associated proteins were tested for the ability to trigger Ca2+ signals in prostate cancer cell lines. Fractions representing the complete repertoire of non-collagenous proteins present in mineralized bone were tested. Results demonstrated that two bone fractions termed D3b- and D4a-triggered Ca2+ signals in prostate cancer cells derived from bone (PC-3), but not brain (DU-145) metastases of prostate cancer. Lymph-node derived LNCaP cells also did not produce a Ca2+ signal in response to addition of soluble bone matrix. No other bone fractions produced a Ca2+ signal in PC-3 cells. It is of interest that bone fractions D3b and D4a contain a number of non-collagenous matrix proteins including osteonectin (SPARC) and osteopontin (OPN), as well as prothrombin. Moreover, antibody LM609 that recognizes the alpha v beta 3 integrin, blocks the ability of OPN to trigger a Ca2+ transient in PC-3 cells. These studies support a conclusion that bone-matrix proteins play a role in the growth and progression of metastatic prostate cancer, and that prior growth in bone may be associated with development of a bone-matrix-responsive phenotype.
Lecrone
V
V
Department of Basic Sciences, University of Texas-Houston, Dental Branch, USA.
Li
W
W
Devoll
R E
RE
Logothetis
C
C
Farach-Carson
M C
MC
D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism; D020013:Calcium Signaling; D005591:Chemical Fractionation; D005456:Fluorescent Dyes / Q000032:analysis; D016257:Fura-2 / Q000032:analysis; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D015676:Osteonectin / Q000494:pharmacology; D053495:Osteopontin; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000556:secondary; D011516:Prothrombin / Q000494:pharmacology; D051381:Rats; D019030:Receptors, Vitronectin / Q000378:metabolism; D012795:Sialoglycoproteins / Q000737:chemistry / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology; D014020:Tissue Extracts / Q000737:chemistry / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D019485:Bone Morphogenetic Proteins; D005456:Fluorescent Dyes; D015676:Osteonectin; D019030:Receptors, Vitronectin; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; C506897:Spp1 protein, rat; D014020:Tissue Extracts; D053495:Osteopontin; D000255:Adenosine Triphosphate; D011516:Prothrombin; D013917:Thrombin; D016257:Fura-2