Abstract
Caveolin-1, a tyrosine-phosphorylated protein, is supposed to have different regulatory roles as promoter or suppressor in many human cancers. However, no published study concerned its expression in benign and malignant salivary gland tumors. The aim of this study was to evaluate and compare the expression of Cav-1 in the most common benign and malignant salivary gland tumors and evaluate its correlation with proliferation activity. In this cross-sectional retrospective study, immunohistochemical expression of caveolin-1 and Ki67 were evaluated in 49 samples, including 11 normal salivary glands, 15 cases of pleomorphic adenoma (PA), 13 adenoid cystic carcinomas (AdCC), and 10 mucoepidermoid carcinomas (MEC). The expression of Cav-1 was seen in 18 % of normal salivary glands and 85 % of tumors. The immunoreaction in the tumors was significantly higher than normal tissues (P = 0.001), but the difference between benign and malignant tumors was not significant (P = 0.07). Expression of Cav-1 was correlated with Ki67 labeling index in PAs, but not in malignant tumors. Cav-1 expression was not in association with tumor size and stage. Overexpression of Cav-1 was found in salivary gland tumors in comparison with normal tissues, but no significant difference was observed between benign and malignant tumors. Cav-1 was inversely correlated with proliferation in PA. Therefore, this marker may participate in tumorigenesis of salivary gland tumors and may be a potential biomarker for cancer treatments.
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs13277-015-3968-z/MediaObjects/13277_2015_3968_Fig1_HTML.gif)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs13277-015-3968-z/MediaObjects/13277_2015_3968_Fig2_HTML.gif)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs13277-015-3968-z/MediaObjects/13277_2015_3968_Fig3_HTML.gif)
Similar content being viewed by others
References
Jaafari-Ashkavandi Z, Ashraf MJ, Moshaverinia M. Salivary gland tumors: a clinicopathologic study of 366 cases in southern Iran. Asian Pac J Cancer Prev. 2013;14(1):27–30.
Stenman G, Persson F, Andersson MK. Diagnostic and therapeutic implications of new molecular biomarkers in salivary gland cancers. Oral Oncol. 2014;50(8):683–90.
Nagao T, Sato E, Inoue R, Oshiro HH, Takahashi R, Nagai T, et al. Immunohistochemical analysis of salivary gland tumors: application for surgical pathology practice. Acta Histochem Cytochem. 2012;45(5):269–82.
Jaafari- Ashkavandi Z, Najvani AD, Tadbir AA, Pardis S, Ranjbar MA, Ashraf MJ. MCM3 as a novel diagnostic marker in benign and malignant salivary gland tumors. Asian Pac J Cancer Prev. 2013;14(6):3479–82.
Hehlgans S, Cordes N. Caveolin-1: an essential modulator of cancer cell radio- and chemoresistance. Am J Cancer Res. 2011;1(4):521–30.
Hung KF, Lin SC, Liu CJ, Chang CS, Chang KW, Kao SY. The biphasic differential expression of the cellular membrane protein, caveolin-1, in oral carcinogenesis. J Oral Pathol Med. 2003;32(8):461–7.
Lajoie P, Nabi RI. Lipid rafts, caveolae, and their endocytosis. Int Rev Cell Mol Biol. 2010;282:135–63.
Yang G, Timme TL, Naruishi K, Fujita T, el Fattah MA, Cao G, et al. Mice with cav-1 gene disruption have benign stromal lesions and compromised epithelial differentiation. Exp Mol Pathol. 2008;84(2):131–40.
Du C, Chen L, Zhang H, Wang Z, Liu W, Xie X, et al. Caveolin-1 limits the contribution of BKCa channel to MCF-7 breast cancer cell proliferation and invasion. Int J Mol Sci. 2014;15(11):20706–22.
Yang G, Addai J, Wheeler TM, Frolov A, Miles BJ, Kadmon D, et al. Correlative evidence that prostate cancer cell-derived caveolin-1 mediates angiogenesis. Hum Pathol. 2007;38(11):1688–95.
Park JH, Ryu JM, Han HJ. Involvement of caveolin-1 in fibronectin-induced mouse embryonic stem cell proliferation: role of FAK, RhoA, PI3K/Akt, and ERK 1/2 pathways. J Cell Physiol. 2011;226(1):267–75.
Goetz JG, Lajoie P, Wiseman SM, Nabi IR. Caveolin-1 in tumor progression: the good, the bad and the ugly. Cancer Metastasis Rev. 2008;27(4):715–35.
Tanase CP, Dima S, Mihai M, Raducan E, Nicolescu MI, Albulescu L, et al. Caveolin-1 overexpression correlates with tumour progression markers in pancreatic ductal adenocarcinoma. J Mol Histol. 2009;40(1):23–9.
Belanger MM, Roussel E, Couet J. Caveolin-1 is down-regulated in human lung carcinoma and acts as a candidate tumor suppressor gene. Chest. 2004;125(5 Suppl):106s.
Wiechen K, Diatchenko L, Agoulnik A, Scharff KM, Schober H, Arlt K, et al. Caveolin-1 is down-regulated in human ovarian carcinoma and acts as a candidate tumor suppressor gene. Am J Pathol. 2001;159(5):1635–43.
Shi L, Chen XM, Wang L, Zhang L, Chen Z. Expression of caveolin-1 in mucoepidermoid carcinoma of the salivary glands: correlation with vascular endothelial growth factor, microvessel density, and clinical outcome. Cancer. 2007;109(8):1523–31.
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(6):2023–34.
Karam JA, Lotan Y, Roehrborn CG, Ashfaq R, Karakiewicz PI, Shariat SF. Caveolin-1 overexpression is associated with aggressive prostate cancer recurrence. Prostate. 2007;67(6):614–22.
Savage K, Lambros MB, Robertson D, Jones RL, Jones C, Mackay A, et al. Caveolin 1 is overexpressed and amplified in a subset of basal-like and metaplastic breast carcinomas: a morphologic, ultrastructural, immunohistochemical, and in situ hybridization analysis. Clin Cancer Res. 2007;13(1):90–101.
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.
Sloan EK, Ciocca DR, Pouliot N, Natoli A, Restall C, Henderson MA, et al. Stromal cell expression of caveolin-1 predicts outcome in breast cancer. Am J Pathol. 2009;174(6):2035–43.
Bissell MJ, Radisky D. Putting tumours in context. Nat Rev Cancer. 2001;1(1):46–54.
Tajika Y, Matsuzaki T, Suzuki T, Aoki T, Hagiwara H, Tanaka S, et al. Immunohistochemical characterization of the intracellular pool of water channel aquaporin-2 in the rat kidney. Anat Sci Int. 2002;77(3):189–95.
Cao G, Yang G, Timme TL, Saika T, Truong LD, Satoh T, et al. Disruption of the caveolin-1 gene impairs renal calcium reabsorption and leads to hypercalciuria and urolithiasis. Am J Pathol. 2003;162(4):1241–8.
Liu X, Wang W, Singh BB, Lockwich T, Jadlowiec J, O’Connell B, et al. Trp1, a candidate protein for the store-operated Ca(2+) influx mechanism in salivary gland cells. J Biol Chem. 2000;275(5):3403–11.
Rathor N, Chung HK, Wang SR, Wang JY, Turner DJ, Rao JN. Caveolin-1 enhances rapid mucosal restitution by activating TRPC1-mediated Ca2+ signaling. Physiol Rep. 2014;3:2(11).
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(3):495–502.
Yerian LM, Anders RA, Tretiakova M, Hart J. Caveolin and thrombospondin expression during hepatocellular carcinogenesis. Am J Surg Pathol. 2004;28(3):357–64.
Kim HA, Kim KH, Lee RA. Expression of caveolin-1 is correlated with Akt-1 in colorectal cancer tissues. Exp Mol Pathol. 2006;80(2):165–70.
Ma WY, Zhuang L, Cai DX, Zhong H, Zhao C, Sun Q. Inverse correlation between caveolin-1 expression and clinical severity in psoriasis vulgaris. J Int Med Res. 2012;40(5):1745–51.
Faggi F, Chiarelli N, Colombi M, Mitola S, Ronca R, Madaro L, et al. Cavin-1 and Caveolin-1 are both required to support cell proliferation, migration and anchorage-independent cell growth in rhabdomyosarcoma. Lab Invest. 2015;95(6):585–602.
Shajahan AN, Wang A, Decker M, Minshall RD, Liu MC, Clarke R. Caveolin-1 tyrosine phosphorylation enhances paclitaxel-mediated cytotoxicity. J Biol Chem. 2007;282(8):5934–43.
Zou H, Volonte D, Galbiati F. Interaction of Caveolin-1 with Ku70 inhibits Bax-mediated apoptosis. PLoS One. 2012;7(6), e39379.
Schwab W, Harada H, Goetz W, Nowicki M, Witt M, Kasper M, et al. Immunocytochemical and biochemical detection of EMMPRIN in the rat tooth germ: differentiation-dependent co-expression with MMPs and co-localization with caveolin-1 in membrane rafts of dental epithelial cells. Histochem Cell Biol. 2007;128(3):195–203.
Jaafari- Ashkavandi Z, Pardis S, Asadzadeh M, Andisheh-Tadbir A, Dehghani-Nazhvani A. Caveolin-1 expression in odontogenic cysts and ameloblastomas. Turk Patoloji Derg. 2014;30(2):94–9.
Ando T, Ishiguro H, Kimura M, Mitsui A, Mori Y, Sugito N, et al. The overexpression of caveolin-1 and caveolin-2 correlates with a poor prognosis and tumor progression in esophageal squamous cell carcinoma. Oncol Rep. 2007;18(3):601–9.
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(6c):4631–7.
Liedtke C, Kersting C, Burger H, Kiesel L, Wulfing P. Caveolin-1 expression in benign and malignant lesions of the breast. World J Surg Oncol. 2007;5:110.
Acknowledgments
The authors thank the Vice-Chancellery of Shiraz University of Medical Science for supporting this research (Grant No. 92-01-03-6272). The authors would like to thank Dr. Sh. Hamedani (DDS, MSc) for helping with the English and editorial assistance in the manuscript and Dr. M. Vossoughi from the Dental Research Development Centre for the statistical analysis. This manuscript is related to the undergraduate thesis of Z. Azizi (Shiraz University of Medical Science, Shiraz, Iran).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Jaafari-Ashkavandi, Z., Ashraf, M.J., Nazhvani, A.D. et al. Caveolin-1 overexpression in benign and malignant salivary gland tumors. Tumor Biol. 37, 1863–1869 (2016). https://doi.org/10.1007/s13277-015-3968-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13277-015-3968-z