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Pathology & Oncology Research
Published in: Pathology & Oncology Research 4/2020

01-10-2020 | Metastasis | Original Article

Caveolin-1 Expression at Metastatic Lymph Nodes Predicts Unfavorable Outcome in Patients with Oral Squamous Cell Carcinoma

Authors: Koroku Kato, Hiroki Miyazawa, Hisano Kobayashi, Natsuyo Noguchi, Daniel Lambert, Shuichi Kawashiri

Published in: Pathology & Oncology Research | Issue 4/2020

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Abstract

We evaluated the clinical and prognostic value of the protein expression of caveolin-1 (CAV1) and p16 at the primary site and metastatic lymph nodes of oral squamous cell carcinoma (OSCC). Primary site specimens from 80 OSCC cases were randomly selected and lymph node specimens from 15 preserved metastatic lymph nodes from among those patients were selected for examination. We evaluated the CAV1 and p16 expression at both the primary site and metastatic lymph nodes, and analyzed the patients’ clinicopathological data in relation to CAV1 and p16 expression. Our analysis revealed significant positive correlations between CAV1 expression at the primary site and pathological metastasis, cell differentiation, and mode of invasion (p = 0.019, p = 0.002, p = 0.015, respectively), but p16 expression was not associated with any clinicopathological factors. Patients with high CAV1 expression at the primary sites showed significantly worse prognoses than those with low or negative CAV1 expression (p = 0.002), and multivariate analysis showed that the T classification and CAV1 expression were independent OSCC prognostic factors. CAV1 expression was also present in the metastatic lymph nodes of the OSCC cases with particularly poor differentiation and high invasive grade, and patients with CAV1-positive metastatic lymph nodes showed significantly worse prognoses than those with CAV1-negative metastatic lymph nodes (p = 0.018). CAV1 may activate metastaticity and the invasive capacity of OSCC cells. CAV1 expression, particularly at metastatic lymph nodes, predicts a worse outcome for OSCC, suggesting that CAV1 could be used as a prognostic marker for OSCC.
Literature
1.
Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, 2002. CA Cancer J Clin 55:74–108PubMed
2.
Vokes EE, Weichselbaum RR, Lippman SM, Hong WK (1993) Head and neck cancer. N Engl J Med 328:184–194PubMed
3.
Forastiere A, Koch W, Trotti A, Sidransky D (2001) Head and neck cancer. N Engl J Med 345:1890–1900PubMed
4.
Yamamoto E, Miyakawa A, Kohama G (1984) Mode of invasion and lymph node metastasis in squamous cell carcinoma of oral cavity. Head Neck 6:939–947
5.
Järvinen AK, Autio R, Kilpinen S, Saarela M, Leivo I, Grénman R, Mäkitie AA, Monni O (2008) High-resolution copy number and gene expression microarray analyses of head and neck squamous cell carcinoma cell lines of tongue and larynx. Genes Chromosom Cancer 47:500–509PubMed
6.
Nakayama S, Sasaki A, Mese H, Alcalde RE, Matsumura T (1998-1999) Establishment of high and low metastasis cell lines derived from a human tongue squamous cell carcinoma. Invasion Metastasis 18:219–228
7.
Wiechen K, Diatchenko L, Agoulnik A, Scharff KM, Schober H, Arlt K, Zhumabayeva B, Siebert PD, Dietel M, Schäfer R, Sers C (2001) Caveolin-1 is down-regulated in human ovarian carcinoma and acts as a candidate tumor suppressor gene. Am J Pathol 159:1635–1643PubMedPubMedCentral
8.
Kato K, Hida Y, Miyamoto M, Hashida H, Shinohara T, Itoh T, Okushiba S, Kondo S, Katoh H (2002) Overexpression of caveolin-1 in esophageal squamous cell carcinoma correlates with lymph node metastasis and pathologic stage. Cancer 94:929–933PubMed
9.
Karam JA, Lotan Y, Roehrborn CG, Ashfaq R, Karakiewicz PI, Shariat SF (2007) Caveolin-1 overexpression is associated with aggressive prostate cancer recurrence. Prostate 67:614–622PubMed
10.
Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tân PF, Westra WH, Chung CH, Jordan RC, Lu C, Kim H, Axelrod R, Silverman CC, Redmond KP, Gillison ML (2010) Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 363:24–35PubMedPubMedCentral
11.
Allen CT, Lewis JS Jr, El-Mofty SK, Haughey BH, Nussenbaum B (2010) Human papillomavirus and oropharynx cancer: biology, detection and clinical implications. Laryngoscope 120:1756–1772PubMed
12.
Marur S, D'Souza G, Westra WH, Forastiere AA (2010) HPV-associated head and neck cancer: a virus-related cancer epidemic. Lancet Oncol 11:781–789PubMedPubMedCentral
13.
Wang MB, Liu IY, Gornbein JA, Nguyen CT (2015) HPV-positive Oropharyngeal carcinoma: a systematic review of treatment and prognosis. Otolaryngol Head Neck Surg 153:758–769PubMed
14.
In (2009) International Union against Cancer, LH Sobin, MK Gospodrowicz, CH Wittekind (eds.). TNM Classification of Malignant Tumours. 7th Ed. Wiley-Liss, New York, NY
15.
Yamamoto E, Kohama G, Sunagawa H, Iwai M, Hiratsuka H (1983) Mode of invasion, bleomycin sensitivity, and clinical course in squamous cell carcinoma of the oral cavity. Cancer 51:2175–2180PubMed
16.
Heiduschka G, Grah A, Oberndorfer F, Kadletz L, Altorjai G, Kornek G, Wrba F, Thurnher D, Selzer E (2015) Improved survival in HPV/p16-positive oropharyngeal cancer patients treated with postoperative radiotherapy. Strahlenther Onkol 191:209–216PubMed
17.
Glenney JR Jr, Zokas L (1989) Novel tyrosine kinase substrates from Rous sarcoma virus-transformed cells are present in the membrane skeleton. J Cell Biol 108:2401–2408PubMed
18.
Rothberg KG, Heuser JE, Donzell WC, Ying YS, Glenney JR, Anderson RG (1992) Caveolin, a protein component of caveolae membrane coats. Cell 68:673–682PubMed
19.
Lu Z, Ghosh S, Wang Z, Hunter T (2003) Downregulation of caveolin-1 function by EGF leads to the loss of E-cadherin, increased transcriptional activity of beta-catenin, and enhanced tumor cell invasion. Cancer Cell 4:499–515PubMed
20.
Burgermeister E, Xing X, Röcken C, Juhasz M, Chen J, Hiber M, Mair K, Shatz M, Liscovitch M, Schmid RM, Ebert MP (2007) Differential expression and function of caveolin-1 in human gastric cancer progression. Cancer Res 67:8519–8526PubMed
21.
Li S, Couet J, Lisanti MP (1996) Src tyrosine kinases, Gα subunits, and H-Ras share a common membrane-anchored scaffolding protein, caveolin. Caveolin binding negatively regulates the auto-activation of Src tyrosine kinases. J Biol Chem 271:29182–29190PubMedPubMedCentral
22.
Couet J, Sargiacomo M, Lisanti MP (1997) Interaction of a receptor tyrosine kinase, EGF-R, with caveolins. Caveolin binding negatively regulates tyrosine and serine/threonine kinase activities. J Biol Chem 272:30429–30438PubMed
23.
Razani B, Zhang XL, Bitzer M, von Gersdorff G, Böttinger EP, Lisanti MP (2001) Caveolin-1 regulates transforming growth factor (TGF)-beta/SMAD signaling through an interaction with the TGF-beta type I receptor. J Biol Chem 276:6727–6738PubMed
24.
Torres VA, Tapia JC, Rodríguez DA, Párraga M, Lisboa P, Montoya M, Leyton L, Quest AF (2006) Caveolin-1 controls cell proliferation and cell death by suppressing expression of the inhibitor of apoptosis protein survivin. J Cell Sci 119(Pt 9):1812–1823PubMed
25.
Goetz JG, Lajoie P, Wiseman SM, Nabi IR (2008) Caveolin-1 in tumor progression: the good, the bad and the ugly. Cancer Metastasis Rev 27:715–735PubMed
26.
Senetta R, Stella G, Pozzi E, Sturli N, Massi D, Cassoni P (2013) Caveolin-1 as a promoter of tumour spreading: when, how, where and why. J Cell Mol Med 17:325–336PubMedPubMedCentral
27.
Fu P, Chen F, Pan Q, Zhao X, Zhao C, Cho WC, Chen H (2017) The different functions and clinical significances of caveolin-1 in human adenocarcinoma and squamous cell carcinoma. Onco Targets Ther 10:819–835PubMedPubMedCentral
28.
Ho CC, Huang PH, Huang HY, Chen YH, Yang PC, Hsu SM (2002) Up-regulated caveolin-1 accentuates the metastasis capability of lung adenocarcinoma by inducing filopodia formation. Am J Pathol 161:1647–1656PubMedPubMedCentral
29.
Chen HL, Fan LF, Gao J, Ouyang JP, Zhang YX (2011) Differential expression and function of the caveolin-1 gene in non-small cell lung carcinoma. Oncol Rep 25:359–366PubMed
30.
Cassoni P, Daniele L, Maldi E, Righi L, Tavaglione V, Novello S, Volante M, Scagliotti GV, Papotti M (2009) Caveolin-1 expression in lung carcinoma varies according to tumour histotype and is acquired de novo in brain metastases. Histopathology 55:20–27PubMed
31.
Ando T, Ishiguro H, Kimura M, Mitsui A, Mori Y, Sugito N, Tomoda K, Mori R, Harada K, Katada T, Ogawa R, Fujii Y, Kuwabara Y (2007) The overexpression of caveolin-1 and caveolin-2 correlates with a poor prognosis and tumor progression in esophageal squamous cell carcinoma. Oncol Rep 18:601–609PubMed
32.
Liu Z, Yu J, Wu R, Tang S, Cai X, Guo G, Chen S (2017) Rho/ROCK pathway regulates migration and invasion of esophageal squamous cell carcinoma by regulating Caveolin-1. Med Sci Monit 23:6174–6185PubMedPubMedCentral
33.
Diaz-Valdivia N, Bravo D, Huerta H, Henriquez S, Gabler F, Vega M, Romero C, Calderon C, Owen GI, Leyton L, Quest AF (2015) Enhanced caveolin-1 expression increases migration, anchorage-independent growth and invasion of endometrial adenocarcinoma cells. BMC Cancer 15:463PubMedPubMedCentral
34.
Yamaguchi H, Takeo Y, Yoshida S, Kouchi Z, Nakamura Y, Fukami K (2009) Lipid rafts and caveolin-1 are required for invadopodia formation and extracellular matrix degradation by human breast cancer cells. Cancer Res 69:8594–8602PubMed
35.
Wang R, Li Z, Guo H, Shi W, Xin Y, Chang W, Huang T (2014) Caveolin 1 knockdown inhibits the proliferation, migration and invasion of human breast cancer BT474 cells. Mol Med Rep 9:1723–1728PubMed
36.
Auzair LB, Vincent-Chong VK, Ghani WM, Kallarakkal TG, Ramanathan A, Lee CE, Rahman ZA, Ismail SM, Abraham MT, Zain RB (2016) Caveolin 1 (Cav-1) and actin-related protein 2/3 complex, subunit 1B (ARPC1B) expressions as prognostic indicators for oral squamous cell carcinoma (OSCC). Eur Arch Otorhinolaryngol 273:1885–1893PubMed
37.
Ketteler J, Klein D (2018) Caveolin-1, cancer and therapy resistance. Int J Cancer 143:2092–2104PubMed
38.
Wang Z, Wang N, Li W, Liu P, Chen Q, Situ H, Zhong S, Guo L, Lin Y, Shen J, Chen J (2014) Caveolin-1 mediates chemoresistance in breast cancer stem cells via β-catenin/ABCG2 signaling pathway. Carcinogenesis 35:2346–2356PubMed
39.
Sun S, Hong SA, Won HS, Yoo SH, Lee HH, Kim O, Ko YH (2017) Prognostic value of metastatic Tumoral Caveolin-1 expression in patients with resected gastric Cancer. Gastroenterol Res Pract 2017:5905173PubMed
40.
Williams TM, Medina F, Badano I, Hazan RB, Hutchinson J, Muller WJ, Chopra NG, Scherer PE, Pestell RG, Lisanti MP (2004) Caveolin-1 gene disruption promotes mammary tumorigenesis and dramatically enhances lung metastasis in vivo. Role of Cav-1 in cell invasiveness and matrix metalloproteinase (MMP-2/9) secretion. J Biol Chem 279:51630–51646PubMed
41.
Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tân PF, Westra WH, Chung CH, Jordan RC, Lu C, Kim H, Axelrod R, Silverman CC, Redmond KP, Gillison ML (2010) Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 363:24–35PubMedPubMedCentral
42.
Namazie A, Alavi S, Olopade OI, Pauletti G, Aghamohammadi N, Aghamohammadi M, Gornbein JA, Calcaterra TC, Slamon DJ, Wang MB, Srivatsan ES (2002) Cyclin D1 amplification and p16(MTS1/CDK4I)deletion correlate with poor prognosis in head and neck tumors. Laryngoscope 112:472–481PubMed
43.
Zafereo ME, Xu L, Dahlstrom KR, Viamonte CA, El-Naggar AK, Wei Q, Li G, Sturgis EM (2016) Squamous cell carcinoma of the oral cavity often overexpresses p16 but is rarely driven by human papillomavirus. Oral Oncol 56:47–53PubMedPubMedCentral
44.
Kouketsu A, Sato I, Abe S, Oikawa M, Shimizu Y, Takahashi T, Kumamoto H (2016) Detection of human papillomavirus infection in oral squamous cell carcinoma: a cohort study of Japanese patients. J Oral Pathol Med 45:565–572PubMed
45.
Götz C, Drecoll E, Straub M, Bissinger O, Wolff KD, Kolk A (2016) Impact of HPV infection on oral squamous cell carcinoma. Oncotarget 7:76704–76712PubMedPubMedCentral
46.
Nopmaneepaisarn T, Tangjaturonrasme N, Rawangban W, Vinayanuwattikun C, Keelawat S, Bychkov A (2019) Low prevalence of p16-positive HPV-related head-neck cancers in Thailand: tertiary referral center experience. BMC Cancer 19:1050PubMedPubMedCentral
47.
Sieczkarski SB, Whittaker GR (2005) Viral entry. Curr Top Microbiol Immunol 285:1–23PubMed
48.
Smith JL, Campos SK, Ozbun MA (2007) Human papillomavirus type 31 uses a caveolin 1- and dynamin 2-mediated entry pathway for infection of human keratinocytes. J Virol 81:9922–9931PubMedPubMedCentral
49.
Smith JL, Campos SK, Wandinger-Ness A, Ozbun MA (2008) Caveolin-1-dependent infectious entry of human papillomavirus type 31 in human keratinocytes proceeds to the endosomal pathway for pH-dependent uncoating. J Virol 82:9505–9512PubMedPubMedCentral
Metadata
Title
Caveolin-1 Expression at Metastatic Lymph Nodes Predicts Unfavorable Outcome in Patients with Oral Squamous Cell Carcinoma
Authors
Koroku Kato
Hiroki Miyazawa
Hisano Kobayashi
Natsuyo Noguchi
Daniel Lambert
Shuichi Kawashiri
Publication date
01-10-2020
Publisher
Springer Netherlands
Keyword
Metastasis
Published in
Pathology & Oncology Research / Issue 4/2020
Print ISSN: 1219-4956
Electronic ISSN: 1532-2807
DOI
https://doi.org/10.1007/s12253-019-00791-1

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