Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ASCO Annual Meeting 2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

2024 ASCO Annual Meeting

Keep up to date with all the top stories and latest evidence with our hub page, including official congress videos and expert takeaways.
ADVANCED SEARCH
Log in
Top
Tumor Biology
Published in: Tumor Biology 5/2012

Open Access 01-10-2012 | Research Article

MCAM is a novel metastasis marker and regulates spreading, apoptosis and invasion of ovarian cancer cells

Authors: Zheng Wu, Zhiyong Wu, Jun Li, Xiaomei Yang, Yahui Wang, Yi Yu, Jun Ye, Congjian Xu, Wenxin Qin, Zhigang Zhang

Published in: Tumor Biology | Issue 5/2012

Login to get access

Abstract

Melanoma cell adhesion molecule (MCAM) is a cell adhesion molecule that is abnormally expressed in a variety of tumours and is closely associated with tumour metastasis. The role of MCAM in ovarian cancer development has not been fully studied. In this study, through immunohistochemical staining of ovarian cancer tissue samples and RNA interference to silence MCAM in ovarian cancer cells, we examined the impact of MCAM on the biological functions of ovarian cancer cells and attempted to reveal the role of MCAM in ovarian cancer development. Our results showed that MCAM expression was particularly high in metastatic ovarian cancers compared with other pathological types of ovarian epithelial tissues. After MCAM silencing in the MCAM high-expression ovarian cancer cell line SKOV-3, the cell apoptosis was increased, whereas the cell spreading and invasion were significantly reduced, which may be related with dysregulation of small RhoGTPase (RhoA and Cdc42).These results suggest that MCAM expression in ovarian cancer is highly correlated with the metastatic potential of the cancer. MCAM is likely to participate in the regulation of the Rho signalling pathway to protect ovarian cancer cells from apoptosis and promote their malignant invasion and metastasis. Therefore, MCAM can be used not only as a molecular marker to determine the prognosis of ovarian cancer but also as a therapeutic target in metastatic ovarian cancer.
Literature
1.
2.
Cavallaro U, Christofori G. Cell adhesion and signalling by cadherins and Ig-CAMs in cancer. Nat Rev Cancer. 2004;4(2):118–32.CrossRefPubMed
3.
Sellar GC, Watt KP, Rabiasz GJ, Stronach EA, Li L, Miller EP, et al. OPCML at 11q25 is epigenetically inactivated and has tumor-suppressor function in epithelial ovarian cancer. Nat Genet. 2003;34(3):337–43.CrossRefPubMed
4.
Furuya M, Kato H, Nishimura N, Ishiwata I, Ikeda H, Ito R, et al. Down-regulation of CD9 in human ovarian carcinoma cell might contribute to peritoneal dissemination: morphologic alteration and reduced expression of beta1 integrin subsets. Cancer Res. 2005;65(7):2617–25.CrossRefPubMed
5.
Patel IS, Madan P, Getsios S, Bertrand MA, MacCalman CD. Cadherin switching in ovarian cancer progression. Int J Cancer. 2003;106(2):172–7.CrossRefPubMed
6.
Lehmann JM, Riethmuller G, Johnson JP. MUC18, a marker of tumor progression in human melanoma, shows sequence similarity to the neural cell adhesion molecules of the immunoglobulin superfamily. Proc Natl Acad Sci. 1989;86(24):9891–5.CrossRefPubMedPubMedCentral
7.
Anfosso F, Bardin N, Vivier E, Sabatier F, Sampol J, Dignat-George F. Outside-in signaling pathway linked to CD146 engagement in human endothelial cells. J Biol Chem. 2001;276(2):1564–9.CrossRefPubMed
8.
Xie S, Luca M, Huang S, Gutman M, Reich R, Johnson JP, et al. Expression of MCAM/MUC18 by human melanoma cells leads to increased tumor growth and metastasis. Cancer Res. 1997;57(11):2295–303.PubMed
9.
Wu GJ, Peng Q, Fu P, Wang SW, Chiang CF, Dillehay DL, et al. Ectopical expression of human MUC18 increases metastasis of human prostate cancer cells. Gene. 2004;327(2):201–13.CrossRefPubMed
10.
Zabouo G, Imbert AM, Jacquemier J, Finetti P, Moreau T, Esterni B, et al. CD146 expression is associated with a poor prognosis in human breast tumors and with enhanced motility in breast cancer cell lines. Breast Cancer Res. 2009;11(1):R1.CrossRefPubMedPubMedCentral
11.
Kristiansen G, Yu Y, Schluns K, Sers C, Dietel M, Petersen I. Expression of the cell adhesion molecule CD146/MCAM in non-small cell lung cancer. Anal Cell Pathol. 2003;25(2):77–81.CrossRefPubMedPubMedCentral
12.
Aldovini D, Demichelis F, Doglioni C, Di Vizio D, Galligioni E, Brugnara S, et al. M-CAM expression as marker of poor prognosis in epithelial ovarian cancer. Int J Cancer. 2006;119(8):1920–6.CrossRefPubMed
13.
Leikin S, Rau DC, Parsegian VA. Direct measurement of forces between self-assembled proteins: temperature-dependent exponential forces between collagen triple helices. Proc Natl Acad Sci USA. 1994;91(1):276–80.CrossRefPubMedPubMedCentral
14.
Li J, Yi SQ, Terayama H, Naito M, Hirai S, Qu N, et al. Distribution of ghrelin-producing cells in stomach and the effects of ghrelin administration in the house musk shrew (Suncus murinus). Neuro Endocrinol Lett. 2010;31(3):406–12.PubMed
15.
Beausoleil MS, Schulze EB, Goodale D, Postenka CO, Allan AL. Deletion of the thrombin cleavage domain of osteopontin mediates breast cancer cell adhesion, proteolytic activity, tumorgenicity, and metastasis. BMC Cancer. 2011;11:25.CrossRefPubMedPubMedCentral
16.
Schmittgen TD, Zakrajsek BA. Effect of experimental treatment on housekeeping gene expression: validation by real-time, quantitative RT-PCR. J Biochem Biophys Methods. 2000;46(1–2):69–81.CrossRefPubMed
17.
Zhang Z, Chometon G, Wen T, Qu H, Mauch C, Krieg T, et al. Migration of epithelial cells on laminins: RhoA antagonizes directionally persistent migration. Eur J Cell Biol. 2011;90(1):1–12.CrossRefPubMed
18.
Zhang ZG, Lambert CA, Servotte S, Chometon G, Eckes B, Krieg T, et al. Effects of constitutively active GTPases on fibroblast behavior. Cell Mol Life Sci. 2006;63(1):82–91.CrossRefPubMedPubMedCentral
19.
Alais S, Allioli N, Pujades C, Duband JL, Vainio O, Imhof BA, et al. HEMCAM/CD146 downregulates cell surface expression of beta1 integrins. J Cell Sci. 2001;114(Pt 10):1847–59.PubMed
20.
Christofori G. Changing neighbours, changing behaviour: cell adhesion molecule-mediated signalling during tumour progression. EMBO J. 2003;22(10):2318–23.CrossRefPubMedPubMedCentral
21.
Sawada K, Mitra AK, Radjabi AR, Bhaskar V, Kistner EO, Tretiakova M, et al. Loss of E-cadherin promotes ovarian cancer metastasis via alpha 5-integrin, which is a therapeutic target. Cancer Res. 2008;68(7):2329–39.CrossRefPubMedPubMedCentral
22.
Friedl P, Gilmour D. Collective cell migration in morphogenesis, regeneration and cancer. Nat Rev Mol Cell Biol. 2009;10(7):445–57.CrossRefPubMed
23.
Wai Wong C, Dye DE, Coombe DR. The role of immunoglobulin superfamily cell adhesion molecules in cancer metastasis. Int J Cell Biol. 2012;340296.
24.
Ouhtit A, Gaur RL, Abd Elmageed ZY, Fernando A, Thouta R, Trappey AK, et al. Towards understanding the mode of action of the multifaceted cell adhesion receptor CD146. Biochim Biophys Acta. 2009;1795(2):130–6.PubMed
25.
Sers C, Kirsch K, Rothbacher U, Riethmuller G, Johnson JP. Genomic organization of the melanoma-associated glycoprotein MUC18: implications for the evolution of the immunoglobulin domains. Proc Natl Acad Sci. 1993;90(18):8514–8.CrossRefPubMedPubMedCentral
26.
Filshie RJ, Zannettino AC, Makrynikola V, Gronthos S, Henniker AJ, Bendall LJ, et al. MUC18, a member of the immunoglobulin superfamily, is expressed on bone marrow fibroblasts and a subset of hematological malignancies. Leukemia. 1998;12(3):414–21.CrossRefPubMed
27.
Wu GJ, Fu P, Wang SW, Wu MW. Enforced expression of MCAM/MUC18 increases in vitro motility and invasiveness and in vivo metastasis of two mouse melanoma K1735 sublines in a syngeneic mouse model. Mol Cancer Res. 2008;6(11):1666–77.CrossRefPubMed
28.
Shih LM, Hsu MY, Palazzo JP, Herlyn M. The cell–cell adhesion receptor Mel-CAM acts as a tumor suppressor in breast carcinoma. Am J Pathol. 1997;151(3):745–51.PubMedPubMedCentral
29.
Watson-Hurst K, Becker D. The role of N-cadherin, MCAM and beta3 integrin in melanoma progression, proliferation, migration and invasion. Cancer Biol Ther. 2006;5(10):1375–82.CrossRefPubMed
30.
Mills L, Tellez C, Huang S, Baker C, McCarty M, Green L, et al. Fully human antibodies to MCAM/MUC18 inhibit tumor growth and metastasis of human melanoma. Cancer Res. 2002;62(17):5106–14.PubMed
31.
Fromigue O, Hamidouche Z, Marie PJ. Blockade of the RhoA-JNK-c-Jun-MMP2 cascade by atorvastatin reduces osteosarcoma cell invasion. J Biol Chem. 2008;283(45):30549–56.CrossRefPubMedPubMedCentral
32.
Wang H, Linghu H, Wang J, Che YL, Xiang TX, Tang WX, et al. The role of Crk/Dock180/Rac1 pathway in the malignant behavior of human ovarian cancer cell SKOV3. Tumour Biol. 2010;31(1):59–67.CrossRefPubMed
33.
Coleman ML, Olson MF. Rho GTPase signalling pathways in the morphological changes associated with apoptosis. Cell Death Differ. 2002;9(5):493–504.CrossRefPubMed
Metadata
Title
MCAM is a novel metastasis marker and regulates spreading, apoptosis and invasion of ovarian cancer cells
Authors
Zheng Wu
Zhiyong Wu
Jun Li
Xiaomei Yang
Yahui Wang
Yi Yu
Jun Ye
Congjian Xu
Wenxin Qin
Zhigang Zhang
Publication date
01-10-2012
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 5/2012
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-012-0417-0

Other articles of this Issue 5/2012

Tumor Biology 5/2012 Go to the issue

Research Article

High RIN1 expression is associated with poor prognosis in patients with gastric adenocarcinoma

Research Article

Rsf-1 overexpression correlates with poor prognosis and cell proliferation in colon cancer

Research Article

Expression of transforming growth factor-β1 (TGF-β1) and E-cadherin in glioma

Research Article

TNF-α and IL-10 promoter polymorphisms, HPV infection, and cervical cancer risk

Research Article

RhoE functions as a tumor suppressor in esophageal squamous cell carcinoma and modulates the PTEN/PI3K/Akt signaling pathway

Research Article

Vaccination with the repeat β-hCG C-terminal peptide carried by heat shock protein-65 (HSP65) for inducing antitumor effects

2024 ASCO Annual Meeting Coverage

Highlights of the Day: Breast cancer – metastatic

Breast Cancer Video

In this session, Dr. Wolff provides his key takeaways from the data presented in the metastatic breast cancer oral abstract session at ASCO 2024.

Watch now

Highlights of the Day: Gynecologic cancer

Gynecologic Cancer Video

Highlights of the Day: Breast Cancer – local/regional/adjuvant

Breast Cancer Video

Neoadjuvant dual immunotherapy improves melanoma outcomes

04-06-2024 Melanoma News

» View more highlights on the ASCO 2024 congress hub page

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits