Vasoactive intestinal peptide induces oxidative stress and suppresses metastatic potential in human clear cell renal cell carcinoma

Vacas, Eva; Bajo, Ana M.; Schally, Andrew V.; Sánchez‐Chapado, Manuel; Prieto, Juan Carlos; Carmena, Marı́a J.

doi:10.1016/j.mce.2012.10.021

Cited by 14 publications

(11 citation statements)

References 48 publications

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“…Despite the development of imaging techniques and surgical innovations, ccRCC carries an extremely high risk of invasiveness and metastasis, with 50% of patients eventually developing metastatic disease (3). Furthermore, ccRCC exhibits resistance to chemotherapy and radiation, and only ~10% of patients suffering from metastatic disease survive for five years following diagnosis (4).…”

Section: Introductionmentioning

confidence: 99%

Decreased expression of Dkk1 and Dkk3 in human clear cell renal cell carcinoma

Guo

Zhang

Yang

et al. 2014

Molecular Medicine Reports

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Abstract. The expression patterns of the Dickkopf (Dkk) family of proteins varies in different cancers. In the present study, the expression levels of Dkk1 and Dkk3 were investigated in clear cell renal cell carcinoma (ccRCC) tissues. Dkk1 and Dkk3 serum levels were also examined in patients with ccRCC, and the association between clinicopathological features and Dkk levels was investigated. Serum Dkk1 and Dkk3 were quantified using ELISA in 64 patients with ccRCC and in 30 healthy individuals (controls). The expression levels of Dkk1 and Dkk3 were analyzed in tumor and adjacent normal tissues obtained from patients with ccRCC (n=20) using quantitative polymerase chain reaction (qPCR), western blot analysis and immunohistochemistry. The mean serum levels of Dkk1 and Dkk3 in the patients with ccRCC were significantly lower than those in the healthy controls. Furthermore, the serum Dkk1 levels were significantly lower at higher tumor-node-metastasis stages and tumor grades. qPCR, western blot analysis and immunohistochemistry revealed a significant decrease in the Dkk1 and Dkk3 mRNA and protein levels in the tumor tissues compared with the adjacent normal tissues. Consequently, Dkk1 and Dkk3 may present a novel molecular target for the diagnosis and therapeutic treatment of ccRCC.

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Section: Introductionmentioning

confidence: 99%

Decreased expression of Dkk1 and Dkk3 in human clear cell renal cell carcinoma

Guo

Zhang

Yang

et al. 2014

Molecular Medicine Reports

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“…The decreased expression of TNFα and IL-6, IL-12 and iNOS after VIP treated required co-culture of TAM and MKN-45. In a previous study, VIP suppressed metastatic human clear cell renal cell carcinoma by inducing oxidative stress (9). Vacas et al demonstrated that VIP inhibited invasion and metastasis of human clear cell renal cell carcinoma via decreasing β-catenin (9).…”

Section: Discussionmentioning

confidence: 97%

“…In a previous study, VIP suppressed metastatic human clear cell renal cell carcinoma by inducing oxidative stress (9). Vacas et al demonstrated that VIP inhibited invasion and metastasis of human clear cell renal cell carcinoma via decreasing β-catenin (9). On the contrary, high expression of VIP in pancreas could induce VIPoma which is a very rare type of cancer that usually derived from pancreatic cells (38).…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have shown that VIP has potential effects on increasing vessel formation in a xenograft model providing insight into VIP treatment in clinical practice (10,20). Similarly, Vacas and colleagues indicated that VIP suppresses clear cell renal cell carcinoma by inducing oxidative stress (9). Therefore, VIP as deactivator of macrophages may also contribute to the suppression of TAM.…”

Section: Introductionmentioning

confidence: 99%

“…In recent studies, VIP was shown to regulate the production of TNFα, IL-6, IL-12 and iNOS (8)(9)(10). Moreover, VIP also inhibits expression levels of cyclooxygenase-2 (COX2) and high mobility group box-1 (HMGB1) in activated macrophages (11,12).…”

Section: Introductionmentioning

confidence: 99%

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Vasoactive intestinal peptide represses activation of tumor-associated macrophages in gastric cancer via regulation of TNFα, IL-6, IL-12 and iNOS

Chen

Yuan

Chen

et al. 2015

International Journal of Oncology

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Abstract. Vasoactive intestinal peptide (VIP) has been regarded as deactivator for macrophages. However, the depressive effect of VIP on tumor-associated macrophages (TAM) has not been recognized. In the present study, we investigated the effect of VIP on gastric cancer via TAM by suppressing expression levels of TNFα, IL-6, IL-12 and iNOS. Real-time PCR was carried out to examine the expression of CD68 to determine the levels of TAM. The effect of VIP on cell activities was assayed by proliferation assay, colony formation and flow cytometry analysis. The co-culture of TAM and human gastric cancer cell line MKN-45 were performed to understand whether the VIP affects the gastric cancer cells via TAM. Further, the tumor formation in a nude mouse model and VIP injection were performed to illustrate the effect on tumor progression in vivo. CD68 was high expressed in gastric cancer indicating high level of TAM in gastric cancer. Treatment with VIP significantly depressed TAM activation. Moreover, the expression of TNFα, IL-6, IL-12 and iNOS in TAM were depressed by VIP treatment, and the VIP treated TAM depressed gastric cancer cells. The experiment in the nude mouse model also suggested that by injection with TAM+VIP, the tumor volume and tumor weight were both decreased significantly. These data suggest that treatment with VIP inhibits gastric cancer.

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Urokinase Plasminogen Activator System in Synovial Fibroblasts from Osteoarthritis Patients: Modulation by Inflammatory Mediators and Neuropeptides

et al. 2013

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Plasminogen activators are specific proteolytic enzymes implicated in a variety of basic biological processes. The expression of the urokinase plasminogen activator system components is increased in some human diseases, including osteoarthritis. We sought to study the effect of two components of the inflamed synovial microenvironment on this system, IL-1β and fibronectin fragments, elucidating whether corticotropin-releasing factor (CRF) and vasoactive intestinal peptide (VIP) neuropeptides modulate it, and analyzing the physiological consequences in joint destruction by measuring matrix metalloproteinases-9 and metalloproteinases-13 levels in osteoarthritis fibroblast-like synoviocytes. We showed that IL-1β and fibronectin fragments stimulated urokinase system contributing to the perpetuation of the destructive cascade in joint. VIP modulated, even at constitutive level, this system, also counteracting the effect of both inflammatory stimuli. However, CRF seemed to be ineffective in controlling the production of these proteinases. Moreover, VIP was able to reduce the constitutive expression of matrix metalloproteinase-13 and the levels of both matrix metalloproteinases after stimulation with the pro-inflammatory stimuli. Our results suggest that the presence of early and later inflammatory mediators, such as IL-1β and fibronectin fragments, increases the urokinase system and the matrix metalloproteinases levels. Whereas CRF did not affect this system, VIP counteracts these actions supporting its therapeutic potential for the treatment of osteoarthritis.

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Vasoactive intestinal peptide induces oxidative stress and suppresses metastatic potential in human clear cell renal cell carcinoma

Cited by 14 publications

References 48 publications

Decreased expression of Dkk1 and Dkk3 in human clear cell renal cell carcinoma

Decreased expression of Dkk1 and Dkk3 in human clear cell renal cell carcinoma

Vasoactive intestinal peptide represses activation of tumor-associated macrophages in gastric cancer via regulation of TNFα, IL-6, IL-12 and iNOS

Urokinase Plasminogen Activator System in Synovial Fibroblasts from Osteoarthritis Patients: Modulation by Inflammatory Mediators and Neuropeptides

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