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

Eva Vacas; Ana M. Bajo; Andrew V. Schally; Manuel Sánchez-Chapado; Juan C. Prieto; María J. Carmena

doi:10.1016/j.mce.2012.10.021

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

Eva Vacas, Ana M. Bajo, Andrew V. Schally, Manuel Sánchez-Chapado, Juan C. Prieto, María J. Carmena

Pathology

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

Abstract

Molecular mechanisms involved in progression of clear-cell renal-cell carcinomas (ccRCCs) are poorly understood. A common genetic mutation found in ccRCC is the loss of the von Hippel-Lindau (VHL) gene, which contributes to cancer progression and metastasis. We investigated VIP effects on metastatic and angiogenic factors in human VHL-null A498 ccRCC and HK2 renal cells. VIP increased adhesion but decreased expression of metalloproteinases, MMP2 and MMP9, as well as cell migration and VEGF expression and secretion in A498 but not in HK2 cells. VIP enhanced ROS levels and decreased nuclear levels of β-catenin and NFκB p50-subunit in A498 cells, suggesting neuropeptide involvement in the observed decrease of metastatic ability in clear-cell carcinoma. VIP effects in A498 cells were blocked by the VPAC_1/2-receptor antagonist JV-1-53. In conclusion, present data point to a role of VIP in preventing invasion and metastasis in ccRCCs and support its potential therapeutic usefulness in this disease.

Original language	English (US)
Pages (from-to)	212-222
Number of pages	11
Journal	Molecular and Cellular Endocrinology
Volume	365
Issue number	2
DOIs	https://doi.org/10.1016/j.mce.2012.10.021
State	Published - Jan 3 2013

Keywords

Cell adhesion
Cell migration
NFκB
Renal cell carcinoma
ROS
VIP

ASJC Scopus subject areas

Endocrinology
Molecular Biology
Biochemistry

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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 C.; Carmena, María J.

In: Molecular and Cellular Endocrinology, Vol. 365, No. 2, 03.01.2013, p. 212-222.

Research output: Contribution to journal › Article › peer-review

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

abstract = "Molecular mechanisms involved in progression of clear-cell renal-cell carcinomas (ccRCCs) are poorly understood. A common genetic mutation found in ccRCC is the loss of the von Hippel-Lindau (VHL) gene, which contributes to cancer progression and metastasis. We investigated VIP effects on metastatic and angiogenic factors in human VHL-null A498 ccRCC and HK2 renal cells. VIP increased adhesion but decreased expression of metalloproteinases, MMP2 and MMP9, as well as cell migration and VEGF expression and secretion in A498 but not in HK2 cells. VIP enhanced ROS levels and decreased nuclear levels of β-catenin and NFκB p50-subunit in A498 cells, suggesting neuropeptide involvement in the observed decrease of metastatic ability in clear-cell carcinoma. VIP effects in A498 cells were blocked by the VPAC1/2-receptor antagonist JV-1-53. In conclusion, present data point to a role of VIP in preventing invasion and metastasis in ccRCCs and support its potential therapeutic usefulness in this disease.",

keywords = "Cell adhesion, Cell migration, NFκB, Renal cell carcinoma, ROS, VIP",

author = "Eva Vacas and Bajo, {Ana M.} and Schally, {Andrew V.} and Manuel S{\'a}nchez-Chapado and Prieto, {Juan C.} and Carmena, {Mar{\'i}a J.}",

note = "Funding Information: This work was supported by the Ministerio de Ciencia e Innovaci{\'o}n (Grant SAF2007-63794), Junta de Comunidades de Castilla la Mancha (Grant PII10-0189-3222), Fundaci{\'o}n Mutua Madrile{\~n}a (Grant 2010-002), and Fundaci{\'o}n Jes{\'u}s Serra (Grupo Catalana de Occidente). ",

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AU - Prieto, Juan C.

AU - Carmena, María J.

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N2 - Molecular mechanisms involved in progression of clear-cell renal-cell carcinomas (ccRCCs) are poorly understood. A common genetic mutation found in ccRCC is the loss of the von Hippel-Lindau (VHL) gene, which contributes to cancer progression and metastasis. We investigated VIP effects on metastatic and angiogenic factors in human VHL-null A498 ccRCC and HK2 renal cells. VIP increased adhesion but decreased expression of metalloproteinases, MMP2 and MMP9, as well as cell migration and VEGF expression and secretion in A498 but not in HK2 cells. VIP enhanced ROS levels and decreased nuclear levels of β-catenin and NFκB p50-subunit in A498 cells, suggesting neuropeptide involvement in the observed decrease of metastatic ability in clear-cell carcinoma. VIP effects in A498 cells were blocked by the VPAC1/2-receptor antagonist JV-1-53. In conclusion, present data point to a role of VIP in preventing invasion and metastasis in ccRCCs and support its potential therapeutic usefulness in this disease.

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