Skip to main content
Top
Published in: Medical Oncology 2/2012

01-06-2012 | Original Paper

Caveolin-1 is related to invasion, survival, and poor prognosis in hepatocellular cancer

Authors: Yu Tang, Xiangtian Zeng, Fei He, Yonghui Liao, Niansong Qian, Masakazu Toi

Published in: Medical Oncology | Issue 2/2012

Login to get access

Abstract

Caveolin-1 is the principal components of caveolae membranes, implicated in oncogenesis and angiogenesis. Until now, its expression and functional significance in hepatocellular carcinoma (HCC) are still unclear. In the present study, we demonstrated that expression of caveolin-1 was markedly upregulated in HCC patients. In addition, increased caveolin-1 expression correlated positively with the histological differentiation, portal venous invasion, hepatic venous invasion, intrahepatic metastases, and recurrence, suggesting a role for caveolin-1 in the progression of HCC. HepG2 cell line was transfected with pcDNA3.1/caveolin-1 to observe the significance of the change in caveolin-1 expression. We showed that caveolin-1 overexpression could not only protect HepG2 cells from apoptosis but also enhance its migration and invasion by upregulating MMP-2, MMP-9, and VEGF expressions. Collectively, our clinical and in vitro data indicate that the status of caveolin-1 expression may be one of causative factors for the invasion and poor prognosis in HCC.
Literature
1.
go back to reference Rampone B, Schiavone B, Confuorto G. Current management of hepatocellular cancer. Curr Oncol Rep. 2010;12:186–92.PubMedCrossRef Rampone B, Schiavone B, Confuorto G. Current management of hepatocellular cancer. Curr Oncol Rep. 2010;12:186–92.PubMedCrossRef
2.
go back to reference Tao K, Qian N, Tang Y, Ti Z, Song W, Cao D, et al. Increased Expression of a Disintegrin and Metalloprotease-9 in Hepatocellular Carcinoma: Implications for Tumor Progression and Prognosis. Jpn J Clin Oncol. 2010;40:645–51.PubMedCrossRef Tao K, Qian N, Tang Y, Ti Z, Song W, Cao D, et al. Increased Expression of a Disintegrin and Metalloprotease-9 in Hepatocellular Carcinoma: Implications for Tumor Progression and Prognosis. Jpn J Clin Oncol. 2010;40:645–51.PubMedCrossRef
3.
go back to reference Shatz M, Liscovitch M. Caveolin-1: a tumor-promoting role in human cancer. Int J Radiat Biol. 2008;84:177–89.PubMedCrossRef Shatz M, Liscovitch M. Caveolin-1: a tumor-promoting role in human cancer. Int J Radiat Biol. 2008;84:177–89.PubMedCrossRef
4.
go back to reference Witkiewicz AK, Dasgupta A, Sotgia F, Mercier I, Pestell RG, Sabel M, et al. An absence of stromal caveolin-1 expression predicts early tumor recurrence and poor clinical outcome in human breast cancers. Am J Pathol. 2009;174:2023–34.PubMedCrossRef Witkiewicz AK, Dasgupta A, Sotgia F, Mercier I, Pestell RG, Sabel M, et al. An absence of stromal caveolin-1 expression predicts early tumor recurrence and poor clinical outcome in human breast cancers. Am J Pathol. 2009;174:2023–34.PubMedCrossRef
5.
go back to reference Wiechen K, Sers C, Agoulnik A, Arlt K, Dietel M, Schlag PM, et al. Down-regulation of caveolin-1, a candidate tumor suppressor gene, in sarcomas. Am J Pathol. 2001;158:833–9.PubMedCrossRef Wiechen K, Sers C, Agoulnik A, Arlt K, Dietel M, Schlag PM, et al. Down-regulation of caveolin-1, a candidate tumor suppressor gene, in sarcomas. Am J Pathol. 2001;158:833–9.PubMedCrossRef
6.
go back to reference Wikman H, Kettunen E, Seppänen JK, Karjalainen A, Hollmén J, Anttila S, et al. Identification of differentially expressed genes in pulmonary adenocarcinoma by using cDNA array. Oncogene. 2002;21:5804–13.PubMedCrossRef Wikman H, Kettunen E, Seppänen JK, Karjalainen A, Hollmén J, Anttila S, et al. Identification of differentially expressed genes in pulmonary adenocarcinoma by using cDNA array. Oncogene. 2002;21:5804–13.PubMedCrossRef
7.
go back to reference Kato K, Hida Y, Miyamoto M, Hashida H, Shinohara T, Itoh T, et al. Overexpression of caveolin-1 in esophageal squamous cell carcinoma correlates with lymph node metastasis and pathologic stage. Cancer. 2002;94:929–33.PubMedCrossRef Kato K, Hida Y, Miyamoto M, Hashida H, Shinohara T, Itoh T, et al. Overexpression of caveolin-1 in esophageal squamous cell carcinoma correlates with lymph node metastasis and pathologic stage. Cancer. 2002;94:929–33.PubMedCrossRef
8.
go back to reference Suzuoki M, Miyamoto M, Kato K, Hiraoka K, Oshikiri T, Nakakubo Y, et al. Impact of caveolin-1 expression on prognosis of pancreatic ductal adenocarcinoma. Br J Cancer. 2002;87:1140–4.PubMedCrossRef Suzuoki M, Miyamoto M, Kato K, Hiraoka K, Oshikiri T, Nakakubo Y, et al. Impact of caveolin-1 expression on prognosis of pancreatic ductal adenocarcinoma. Br J Cancer. 2002;87:1140–4.PubMedCrossRef
9.
go back to reference Cokakli M, Erdal E, Nart D, Yilmaz F, Sagol O, Kilic M, et al. Differential expression of Caveolin-1 in hepatocellular carcinoma: correlation with differentiation state, motility and invasion. BMC Cancer. 2009;9:65. Cokakli M, Erdal E, Nart D, Yilmaz F, Sagol O, Kilic M, et al. Differential expression of Caveolin-1 in hepatocellular carcinoma: correlation with differentiation state, motility and invasion. BMC Cancer. 2009;9:65.
10.
go back to reference Zhang ZB, Cai L, Zheng SG, Xiong Y, Dong JH. Overexpression of caveolin-1 in hepatocellular carcinoma with metastasis and worse prognosis: correlation with vascular endothelial growth factor, microvessel density and unpaired artery. Pathol Oncol Res. 2009;15:495–502.PubMedCrossRef Zhang ZB, Cai L, Zheng SG, Xiong Y, Dong JH. Overexpression of caveolin-1 in hepatocellular carcinoma with metastasis and worse prognosis: correlation with vascular endothelial growth factor, microvessel density and unpaired artery. Pathol Oncol Res. 2009;15:495–502.PubMedCrossRef
11.
go back to reference Song W, Tao K, Li H, Jin C, Song Z, Li J, et al. Bmi-1 is related to proliferation, survival and poor prognosis in pancreatic cancer. Cancer Sci. 2010;101:1754–60.PubMedCrossRef Song W, Tao K, Li H, Jin C, Song Z, Li J, et al. Bmi-1 is related to proliferation, survival and poor prognosis in pancreatic cancer. Cancer Sci. 2010;101:1754–60.PubMedCrossRef
12.
13.
go back to reference Joo HJ, Oh DK, Kim YS, Lee KB, Kim SJ. Increased expression of caveolin-1 and microvessel density correlates with metastasis and poor prognosis in clear cell renal cell carcinoma. BJU Int. 2004;93:291–6.PubMedCrossRef Joo HJ, Oh DK, Kim YS, Lee KB, Kim SJ. Increased expression of caveolin-1 and microvessel density correlates with metastasis and poor prognosis in clear cell renal cell carcinoma. BJU Int. 2004;93:291–6.PubMedCrossRef
14.
go back to reference Barresi V, Cerasoli S, Tuccari G. Correlative evidence that tumor cell-derived caveolin-1 mediates angiogenesis in meningiomas. Neuropathology. 2008;28:472–8.PubMedCrossRef Barresi V, Cerasoli S, Tuccari G. Correlative evidence that tumor cell-derived caveolin-1 mediates angiogenesis in meningiomas. Neuropathology. 2008;28:472–8.PubMedCrossRef
15.
go back to reference Moon KC, Lee GK, Yoo SH, Jeon YK, Chung JH, Han J, et al. Expression of caveolin-1 in pleomorphic carcinoma of the lung is correlated with a poor prognosis. Anticancer Res. 2005;25:4631–7.PubMed Moon KC, Lee GK, Yoo SH, Jeon YK, Chung JH, Han J, et al. Expression of caveolin-1 in pleomorphic carcinoma of the lung is correlated with a poor prognosis. Anticancer Res. 2005;25:4631–7.PubMed
16.
go back to reference Choi HN, Kim KR, Park HS, Jang KY, Kang MJ, Lee DG, et al. Expression of caveolin in hepatocellular carcinoma: association with unpaired artery formation and radiologic findings. Korean J Hepatol. 2007;13:396–408.PubMedCrossRef Choi HN, Kim KR, Park HS, Jang KY, Kang MJ, Lee DG, et al. Expression of caveolin in hepatocellular carcinoma: association with unpaired artery formation and radiologic findings. Korean J Hepatol. 2007;13:396–408.PubMedCrossRef
17.
go back to reference Yerian LM, Anders RA, Tretiakova M, Hart J. Caveolin and thrombospondin expression during hepatocellular carcinogenesis. Am J Surg Pathol. 2004;28:357–64.PubMedCrossRef Yerian LM, Anders RA, Tretiakova M, Hart J. Caveolin and thrombospondin expression during hepatocellular carcinogenesis. Am J Surg Pathol. 2004;28:357–64.PubMedCrossRef
18.
go back to reference Zhou H, Jia L, Wang S, Wang H, Chu H, Hu Y, et al. Divergent expression and roles for caveolin-1 in mouse hepatocarcinoma cell lines with varying invasive ability. Biochem Biophys Res Commun. 2006;345:486–94.PubMedCrossRef Zhou H, Jia L, Wang S, Wang H, Chu H, Hu Y, et al. Divergent expression and roles for caveolin-1 in mouse hepatocarcinoma cell lines with varying invasive ability. Biochem Biophys Res Commun. 2006;345:486–94.PubMedCrossRef
19.
go back to reference Zhao X, Liu Y, Ma Q, Wang X, Jin H, Mehrpour M, et al. Caveolin-1 negatively regulates TRAIL-induced apoptosis in human hepatocarcinoma cells. Biochem Biophys Res Commun. 2009;378:21–6.PubMedCrossRef Zhao X, Liu Y, Ma Q, Wang X, Jin H, Mehrpour M, et al. Caveolin-1 negatively regulates TRAIL-induced apoptosis in human hepatocarcinoma cells. Biochem Biophys Res Commun. 2009;378:21–6.PubMedCrossRef
20.
go back to reference Liu J, Lee P, Galbiati F, Kitsis RN, Lisanti MP. Caveolin-1 expression sensitizes fibroblastic and epithelial cells to apoptotic stimulation. Am J Physiol Cell Physiol. 2001;280:C823–35.PubMed Liu J, Lee P, Galbiati F, Kitsis RN, Lisanti MP. Caveolin-1 expression sensitizes fibroblastic and epithelial cells to apoptotic stimulation. Am J Physiol Cell Physiol. 2001;280:C823–35.PubMed
21.
go back to reference Ingueneau C, Huynh-Do U, Thiers JC, Nègre-Salvayre A, Salvayre R, Vindis C. Caveolin-1 sensitizes vascular smooth muscle cells to mildly oxidized LDL-induced apoptosis. Biochem Biophys Res Commun. 2008;369:889–93.PubMedCrossRef Ingueneau C, Huynh-Do U, Thiers JC, Nègre-Salvayre A, Salvayre R, Vindis C. Caveolin-1 sensitizes vascular smooth muscle cells to mildly oxidized LDL-induced apoptosis. Biochem Biophys Res Commun. 2008;369:889–93.PubMedCrossRef
22.
go back to reference Chuang MJ, Sun KH, Tang SJ, Deng MW, Wu YH, Sung JS, et al. Tumor-derived tumor necrosis factor-alpha promotes progression and epithelial-mesenchymal transition in renal cell carcinoma cells. Cancer Sci. 2008;99:905–13.PubMedCrossRef Chuang MJ, Sun KH, Tang SJ, Deng MW, Wu YH, Sung JS, et al. Tumor-derived tumor necrosis factor-alpha promotes progression and epithelial-mesenchymal transition in renal cell carcinoma cells. Cancer Sci. 2008;99:905–13.PubMedCrossRef
23.
go back to reference Sotgia F, Williams TM, Schubert W, Medina F, Minetti C, Pestell RG, et al. Caveolin-1 deficiency (-/-) conveys premalignant alterations in mammary epithelia, with abnormal lumen formation, growth factor independence, and cell invasiveness. Am J Pathol. 2006;168:292–309.PubMedCrossRef Sotgia F, Williams TM, Schubert W, Medina F, Minetti C, Pestell RG, et al. Caveolin-1 deficiency (-/-) conveys premalignant alterations in mammary epithelia, with abnormal lumen formation, growth factor independence, and cell invasiveness. Am J Pathol. 2006;168:292–309.PubMedCrossRef
24.
go back to reference Schoenleber SJ, Kurtz DM, Talwalkar JA, Roberts LR, Gores GJ. Prognostic role of vascular endothelial growth factor in hepatocellular carcinoma: systematic review and meta-analysis. Br J Cancer. 2009;100:1385–92.PubMedCrossRef Schoenleber SJ, Kurtz DM, Talwalkar JA, Roberts LR, Gores GJ. Prognostic role of vascular endothelial growth factor in hepatocellular carcinoma: systematic review and meta-analysis. Br J Cancer. 2009;100:1385–92.PubMedCrossRef
25.
go back to reference Watanabe M, Yang G, Cao G, Tahir SA, Naruishi K, Tabata K, et al. Functional analysis of secreted caveolin-1 in mouse models of prostate cancer progression. Mol Cancer Res. 2009;7:1446–55.PubMedCrossRef Watanabe M, Yang G, Cao G, Tahir SA, Naruishi K, Tabata K, et al. Functional analysis of secreted caveolin-1 in mouse models of prostate cancer progression. Mol Cancer Res. 2009;7:1446–55.PubMedCrossRef
26.
go back to reference Bist A, Fielding PE, Fielding CJ. Two sterol regulatory element-like sequences mediate up-regulation of caveolin gene transcription in response to low density lipoprotein free cholesterol. Proc Natl Acad Sci USA. 1997;94:10693–8.PubMedCrossRef Bist A, Fielding PE, Fielding CJ. Two sterol regulatory element-like sequences mediate up-regulation of caveolin gene transcription in response to low density lipoprotein free cholesterol. Proc Natl Acad Sci USA. 1997;94:10693–8.PubMedCrossRef
27.
go back to reference Wu D, Terrian DM. Regulation of caveolin-1 expression and secretion by a protein kinase cepsilon signaling pathway in human prostate cancer cells. J Biol Chem. 2002;277:40449–55.PubMedCrossRef Wu D, Terrian DM. Regulation of caveolin-1 expression and secretion by a protein kinase cepsilon signaling pathway in human prostate cancer cells. J Biol Chem. 2002;277:40449–55.PubMedCrossRef
28.
go back to reference Salatino M, Beguelin W, Peters MG, Carnevale R, Proietti CJ, Galigniana MD, et al. Progestin-induced caveolin-1 expression mediates breast cancer cell proliferation. Oncogene. 2006;25:7723–39.PubMedCrossRef Salatino M, Beguelin W, Peters MG, Carnevale R, Proietti CJ, Galigniana MD, et al. Progestin-induced caveolin-1 expression mediates breast cancer cell proliferation. Oncogene. 2006;25:7723–39.PubMedCrossRef
Metadata
Title
Caveolin-1 is related to invasion, survival, and poor prognosis in hepatocellular cancer
Authors
Yu Tang
Xiangtian Zeng
Fei He
Yonghui Liao
Niansong Qian
Masakazu Toi
Publication date
01-06-2012
Publisher
Springer US
Published in
Medical Oncology / Issue 2/2012
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-011-9900-5

Other articles of this Issue 2/2012

Medical Oncology 2/2012 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.