Effects of the calciotrophic peptides calcitonin and parathyroid hormone on prostate cancer growth and chemotaxis

Abstract

BACKGROUND.The most common site of metastases in prostate cancer is the skeleton and occurs in 70-80% of patients with prostate carcinoma. Calciotrophic peptides are important in the growth and development of normal bone matrix. METHODS. Three human prostate carcinoma cells lines, DU-145, PC-3, and LNCaP, were exposed to varying concentrations of parathyroid hormone (PTH) or calcitonin (CT). Cell proliferation and chemotaxis were assessed. RESULTS. Proliferation increased in LNCaP cells in a dose-dependent manner following treatment with PTH. Proliferation was not altered in PC-3 cells in response to PTH. Proliferation was decreased in DU-145 and PC-3 cells and increased in LNCaP cells after treatment with CT. Cell chemotaxis was increased in the presence of PTH in DU-145 and PC-3 cells compared to vehicle-treated controls. CONCLUSIONS. The combined proliferation and chemotaxis data suggest that PTH has a dual role in prostate carcinoma resulting in an increase in the number and migration of selected prostate cancer cells. With CT, chemotaxis was unchanged in the DU-145 and PC-3 cells and significantly elevated in the LNCaP cell line. The calciotrophic hormones, PTH and CT, may play an integral role in the regulation of prostate cell growth and metastases.

Calcitonin promotes in vivo metastasis of prostate cancer cells by altering cell signaling, adhesion, and inflammatory pathways

“…Moreover, the abundance of CT/CTR mRNA correlates positively with Gleason grade of primary PCs. In addition, exogenous CT or enforced activation of CT-CTR autocrine axis causes increased tumorigenicity, invasiveness, and resistance to apoptosis in several PC cell lines (Ritchie et al 1997, Nagakawa et al 1998, Sabbisetti et al 2005b, Thomas & Shah 2005, Thomas et al 2006). However, the pathological significance of CT expression in progression of PC from localized tumor to its metastatic form has not been established.…”

“…Although we and others have also demonstrated stimulatory effect of CT on in vitro invasiveness of PC cell lines, we did not examine whether this translates into the formation of distant metastases (Ritchie et al 1997, Sabbisetti et al 2005b, Thomas et al 2006. To examine the role of CT in the process of tumor metastasis, we first stably activated or silenced CT-CTR axis in three PC cell lines by either enforcing the expression of CT in LNCaP cells and CTR in PC-3 cells or by knocking down CT expression in PC-3M cells.…”

Effect of prostatic neuropeptides on migration of prostate cancer cell lines

“…23 Parathyroid hormone (PTH), which has some affinity to the PTH/PTH-rP receptor, also increased proliferation in DU-145 and LNCaP cells and increased chemotaxis in PC-3, DU-145 and LNCaP cells. 24 In the present study, PTH-rP enhanced the haptotactic migration of DU-145 and TSU-pr1 cells. These results indicate that PTH and PTH-rP may play a role in the regulation of growth and invasion of prostate cancer cells.…”

Calcitonin stimulates the secretion of urokinase‐type plasminogen activator from prostate cancer cells: Its possible implications on tumor cell invasion

“…23 Since CT also produced similar effect on invasiveness of LNCaP cells, it is very likely that the stimulatory effect of CT on invasion of PC cells is not affected by the presence or absence of androgen receptor. 22,23 These results are consistent with several studies in renal cell models that have demonstrated that agents that increase cAMP such as cholera toxin, peptide hormones such as vasopressin and CT, as well as membrane-permeable cAMP analogues, can induce high levels of uPA mRNA expression in LLC-PK1 cell line without the need for new protein synthesis. [52][53][54][55][56][57] Since CT has been shown to increase the invasiveness of PC-3M cells, 23 we wanted to test the role of uPA in CT-induced cell invasion.…”

“…18 CT and CT receptors (CTRs) have also been identified in several established PC cell lines such as LNCaP, PC-3, DU-145 and PC-3M. [19][20][21][22] Exogenously added CT stimulates the proliferation of LNCaP cells by stimulating cAMP accumulation and increasing cytoplasmic Ca 21 transients, and stimulates invasion by activating protein kinase A-mediated mechanisms. 19,23 Urokinase-type plasminogen activator (uPA), a member of the serine protease family, is strongly implicated as a promoter of tumor progression in various human malignancies, including breast cancer and PC.…”