Bombesin-Dependent Pro-MMP-9 Activation in Prostatic Cancer Cells Requires β1 Integrin Engagement

Festuccia, Claudio; Angelucci, Adriano; Gravina, Giovanni Luca; Eleuterio, Enrica; Vicentini, Carlo; Bologna, Mauro

doi:10.1006/excr.2002.5609

Cited by 23 publications

(15 citation statements)

References 36 publications

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“…BBS also enhances invasion of Isreco1 colon carcinoma cells through unidentified effector proteins downstream the Rho signaling pathway (Saurin et al, 2002). Moreover, BBS has been proved to induce the expression and activation of the extracellular matrix proteinases urokinase-type plasminogen activator and metalloproteinase-9, as well as the proangiogenic factors interleukin-8 and vascular endothelial growth factor, linked to increased metastatic potential in prostate cancer cells (Festuccia et al, 1998(Festuccia et al, , 2002Levine et al, 2003). In addition, our results show the involvement of NFAT-mediated induction of genes implicated in tumor progression such as Cox-2 in the pro-tumoral effects of BBS.…”

Section: Discussionmentioning

confidence: 99%

Bombesin induces cyclooxygenase-2 expression through the activation of the nuclear factor of activated T cells and enhances cell migration in Caco-2 colon carcinoma cells

et al. 2006

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Cyclooxygenase-2 (Cox-2), the gastrin-release peptide (GRP) and its cognate receptor (GRP-R) are overexpressed in a significant percentage of colorectal carcinomas and are associated with cell growth, invasiveness and tumor progression. However, a molecular link between all of them in adenocarcinomas has not been established. Here, we show that bombesin (BBS), a GRP homolog, stimulates the expression of Cox-2 mRNA and protein in human colon adenocarcinoma Caco-2 cells, resulting in enhanced release of prostaglandin E 2 . These effects were markedly inhibited by the specific BBS antagonist RC-3940-II. BBS promotes the activation of the nuclear factor of activated T cells (NFAT) through a Ca 2 þ /calcineurin (Cn)-linked pathway. Upon BBS stimulation, the NFATc1 isoform translocates into the nucleus with a concomitant increase in NFATc1 binding to two specific recognition sites in the promoter region of the Cox-2 gene. Furthermore, inhibition of Cn activity by the immunosuppressive drug cyclosporin A impaired NFAT activation and diminished Cox-2 expression in BBSstimulated cells. Interestingly, BBS pretreatment strongly enhances the invasive capacity of carcinoma cells, effect which was inhibited by a Cox-2-specific inhibitor. These findings provide the first evidence for the involvement of the Ca 2 þ /Cn/NFAT pathway in BBS-mediated induction of genes involved in colon carcinoma invasiveness such as Cox-2. Oncogene (2007) 26, 958-969.

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Section: Discussionmentioning

confidence: 99%

Bombesin induces cyclooxygenase-2 expression through the activation of the nuclear factor of activated T cells and enhances cell migration in Caco-2 colon carcinoma cells

et al. 2006

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“…Prostate cancer cells secrete a variety of proangiogenic substances, including vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), and extracellular matrix proteinases (5)(6)(7)(8). It has been proposed that neovascularization begins in benign prostatic hyperplasia and keeps progressing in a stepwise fashion in proliferative premalignant and malignant stages (9,10).…”

Section: Introductionmentioning

confidence: 99%

Calcitonin Stimulates Multiple Stages of Angiogenesis by Directly Acting on Endothelial Cells

et al. 2005

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Although a strong correlation between neuroendocrine differentiation and angiogenesis of prostate cancer has been reported, no mechanistic link between the two events has been established. Because neuropeptide calcitonin is secreted by prostate tumors and endothelial cells are known to express calcitonin receptor-like receptor, we examined the potential action of calcitonin on endothelial cells. The presence of calcitonin receptor, calcitonin receptor-like receptor, and receptor activity-modifying proteins in human microvessel endothelial-1 cells was tested by reverse transcriptase-PCR (RT-PCR). The proangiogenic action of calcitonin was examined in several in vitro models of angiogenesis using HMEC-1 cells and also in vivo using dorsal skinfold assays. Calcitonin expression of PC-3M cells was modulated, and its effect on angiogenesis was examined in in vitro as well as in vivo models. The results of RT-PCR and radioligand receptor assays showed the presence of functional calcitonin receptor in HMEC-1 cells. Calcitonin stimulated all phases of angiogenesis through the calcitonin receptor, but its effect on tube morphogenesis by endothelial cells occurred at the concentration of the K d of calcitonin receptor. Silencing of calcitonin receptor expression in HMEC-1 cells abolished calcitonin-induced tube formation. Vascular endothelial growth factor antibodies attenuated but did not abolish calcitonin-induced tube morphogenesis. PC-3M prostate cancer cells induced angiogenesis in in vivo and in vitro models. Overexpression of calcitonin in PC-3M cells increased their angiogenic activity, whereas the silencing of calcitonin expression abolished it. These results show that prostate tumor-derived calcitonin may play an important role in prostate tumor growth by regulating intratumoral vascularization. (Cancer Res 2005; 65(18): 8519-29)

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“…We also found that uPA and MMP-7 were positively correlated in gastric cancer. Evidence suggested that uPA was a crucial factor for regulating the activity of MMP, activating pro-MMP by combination with integrin-β1 and triggering MMP to degrade extracellular matrix components [16] . In addition, maspin and MMP-7 were negatively correlated.…”

Section: Discussionmentioning

confidence: 99%

Expression of maspin, uPA and MMP-7 in human gastric carcinoma

Deng

Yang

et al. 2008

Chin. J. Cancer Res.

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Objective: To investigate the expression of maspin, uPA and MMP-7 in gastric carcinoma and discuss their roles in tumorigenesis and progression of gastric cancer. Methods: Immunohistochemistry SP method was used to detect expression of maspin, uPA and MMP-7 in gastric adenocarcinoma (n=30), signet-ring cell carcinoma (n=30), normal gastric mucosa (n=20); in addition, reverse transcriptase PCR was carried out to compare the mRNA expression of maspin between gastric adenocarcinoma and normal mucosa. Results: The expression rates of maspin, uPA and MMP-7 protein were 50%, 70% and 80% in gastric adenocarcinoma, and 46.7%, 76.7%, and 90% in signet-ring cell carcinoma, respectively. However, the expression rates of maspin, uPA, and MMP-7 protein were 90%, 35% and 30%, respectively in normal gastric mucosa. The relative transcription level of maspin mRNA in normal gastric mucosa was higher than that in gastric adenocarcinoma (P<0.01). Maspin protein expression was significantly related to the depth of invasion and lymph node metastasis of gastric carcinoma, but did not relate to tumor size and TNM staging. The protein expression of uPA and MMP-7 were significantly related to invasive depth, lymph node metastasis and TNM staging of carcinoma, but not to tumor size. Maspin protein expression had a negative correlation with uPA and MMP-7, while uPA protein expression had a positive correlation with MMP-7. The relative mRNA transcription level of Maspin significantly correlated with the lymph node metastasis and the depth of invasion of carcinoma, but did not relate to TNM staging or tumor size. Conclusion: Down-regulated expression of maspin and up-regulated expression of uPA and MMP-7 play important roles in the invasion and metastasis of gastric carcinoma. They may serve as effective markers of the biopathological behavior of gastric tumor.

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Bombesin-Dependent Pro-MMP-9 Activation in Prostatic Cancer Cells Requires β1 Integrin Engagement

Cited by 23 publications

References 36 publications

Bombesin induces cyclooxygenase-2 expression through the activation of the nuclear factor of activated T cells and enhances cell migration in Caco-2 colon carcinoma cells

Bombesin induces cyclooxygenase-2 expression through the activation of the nuclear factor of activated T cells and enhances cell migration in Caco-2 colon carcinoma cells

Calcitonin Stimulates Multiple Stages of Angiogenesis by Directly Acting on Endothelial Cells

Expression of maspin, uPA and MMP-7 in human gastric carcinoma

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