Calcium signals in prostate cancer cells: specific activation by bone-matrix proteins

被引:39
作者
Lecrone, V
Li, W
Devoll, RE
Logothetis, C
Farach-Carson, MC
机构
[1] Univ Delaware, Dept Biol Sci, Newark, DE 19716 USA
[2] Univ Texas, Dept Basic Sci, Dent Branch, Houston, TX USA
[3] Univ Texas, MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Houston, TX 77030 USA
关键词
D O I
10.1054/ceca.1999.0083
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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+], 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, (C) Harcourt Publishers Ltd 2000.
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页码:35 / 42
页数:8
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