CD9P-1 Expression Correlates with the Metastatic Status of Lung Cancer, and a Truncated Form of CD9P-1, GS-168AT2, Inhibits in Vivo Tumour Growth

Overview

Journal Br J Cancer

Specialty Oncology

Date 2011 Jan 6

PMID 21206492

Citations 14

Authors

W Guilmain

S Colin

E Legrand

J P Vannier

C Steverlynck

M Bongaerts

M Vasse

S Al-Mahmood

Affiliations

Soon will be listed here.

Abstract

Background: Loss of CD9 expression has been correlated with a higher motility and metastatic potential of tumour cells originating from different organs. However, the mechanism underlying this loss is not yet understood.

Methods: We produced a truncated form of partner 1 of CD9 (CD9P-1), GS-168AT2, and developed a new monoclonal antibody directed towards the latter. We measured the expression of CD9 and CD9P-1 in human lung tumours (hLTs), and monitored the level of CD9 in NCI-H460, in vitro and in vivo, in the presence and absence of GS-168AT2.

Results: Loss of CD9 is inversely related to the expression of CD9P-1, which correlates with the metastatic status of hLT (n=55). In vitro, GS-168AT2 is rapidly internalised and degraded at both the membrane and cytoplasm of NCI-H460, and this correlates with the association of GS-168AT2 with both CD9 and CD81. Intraperitoneal injections of GS-168AT2 in NCI-H460-xenografted Nude mice led to drastic inhibition of tumour growth, as well as to the downregulation of CD9, but not of CD81, in the tumour core.

Conclusion: These findings show for the first time that CD9P-1 expression positively correlates with the metastatic status of hLT, and that the upregulation of CD9P-1 expression could be one of the mechanisms underlying the loss of CD9 in solid tumours. Our study also reveals that, under certain conditions, loss of CD9 could be a tumour growth-limiting phenomenon rather than a tumour growth-promoting one.

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References

Chambrion C, Le Naour F . The tetraspanins CD9 and CD81 regulate CD9P1-induced effects on cell migration. PLoS One. 2010; 5(6):e11219. PMC: 2888588. DOI: 10.1371/journal.pone.0011219. View

Uchida S, Shimada Y, Watanabe G, Li Z, Hong T, Miyake M . Motility-related protein (MRP-1/CD9) and KAI1/CD82 expression inversely correlate with lymph node metastasis in oesophageal squamous cell carcinoma. Br J Cancer. 1999; 79(7-8):1168-73. PMC: 2362236. DOI: 10.1038/sj.bjc.6690186. View

Lazo P . Functional implications of tetraspanin proteins in cancer biology. Cancer Sci. 2007; 98(11):1666-77. PMC: 11159418. DOI: 10.1111/j.1349-7006.2007.00584.x. View

Stipp C, Orlicky D, Hemler M . FPRP, a major, highly stoichiometric, highly specific CD81- and CD9-associated protein. J Biol Chem. 2000; 276(7):4853-62. DOI: 10.1074/jbc.M009859200. View

Boucheix C, Duc G, Jasmin C, Rubinstein E . Tetraspanins and malignancy. Expert Rev Mol Med. 2004; 2001:1-17. DOI: 10.1017/S1462399401002381. View

Wang X, Liu T, Zhu C, Li Y, Sun R, Sun C . [Expression of KAI1, MRP-1, and FAK proteins in lung cancer detected by high-density tissue microarray]. Ai Zheng. 2005; 24(9):1091-5. View

Takeda Y, He P, Tachibana I, Zhou B, Miyado K, Kaneko H . Double deficiency of tetraspanins CD9 and CD81 alters cell motility and protease production of macrophages and causes chronic obstructive pulmonary disease-like phenotype in mice. J Biol Chem. 2008; 283(38):26089-97. PMC: 3258854. DOI: 10.1074/jbc.M801902200. View

Kusukawa J, Ryu F, Kameyama T, Mekada E . Reduced expression of CD9 in oral squamous cell carcinoma: CD9 expression inversely related to high prevalence of lymph node metastasis. J Oral Pathol Med. 2001; 30(2):73-9. DOI: 10.1034/j.1600-0714.2001.300202.x. View

Adachi M, Taki T, Konishi T, Huang C, Higashiyama M, Miyake M . Novel staging protocol for non-small-cell lung cancers according to MRP-1/CD9 and KAI1/CD82 gene expression. J Clin Oncol. 1998; 16(4):1397-406. DOI: 10.1200/JCO.1998.16.4.1397. View

10.

Charrin S, Le Naour F, Silvie O, Milhiet P, Boucheix C, Rubinstein E . Lateral organization of membrane proteins: tetraspanins spin their web. Biochem J. 2009; 420(2):133-54. DOI: 10.1042/BJ20082422. View

11.

Vidal-Laliena M, Romero X, March S, Requena V, Petriz J, Engel P . Characterization of antibodies submitted to the B cell section of the 8th Human Leukocyte Differentiation Antigens Workshop by flow cytometry and immunohistochemistry. Cell Immunol. 2005; 236(1-2):6-16. DOI: 10.1016/j.cellimm.2005.08.002. View

12.

Yunta M, Lazo P . Tetraspanin proteins as organisers of membrane microdomains and signalling complexes. Cell Signal. 2003; 15(6):559-64. DOI: 10.1016/s0898-6568(02)00147-x. View

13.

Maecker H, Todd S, Levy S . The tetraspanin superfamily: molecular facilitators. FASEB J. 1997; 11(6):428-42. View

14.

Orlicky D, Lieber J, Morin C, Evans R . Synthesis and accumulation of a receptor regulatory protein associated with lipid droplet accumulation in 3T3-L1 cells. J Lipid Res. 1998; 39(6):1152-61. View

15.

Dignam J, Lebovitz R, Roeder R . Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983; 11(5):1475-89. PMC: 325809. DOI: 10.1093/nar/11.5.1475. View

16.

Zoller M . Tetraspanins: push and pull in suppressing and promoting metastasis. Nat Rev Cancer. 2008; 9(1):40-55. DOI: 10.1038/nrc2543. View

17.

Hemler M . Tetraspanin functions and associated microdomains. Nat Rev Mol Cell Biol. 2005; 6(10):801-11. DOI: 10.1038/nrm1736. View

18.

Orlicky D . Negative regulatory activity of a prostaglandin F2 alpha receptor associated protein (FPRP). Prostaglandins Leukot Essent Fatty Acids. 1996; 54(4):247-59. DOI: 10.1016/s0952-3278(96)90055-1. View

19.

Chen M, Tung K, Coonrod S, Takahashi Y, Bigler D, Chang A . Role of the integrin-associated protein CD9 in binding between sperm ADAM 2 and the egg integrin alpha6beta1: implications for murine fertilization. Proc Natl Acad Sci U S A. 1999; 96(21):11830-5. PMC: 18372. DOI: 10.1073/pnas.96.21.11830. View

20.

Houle C, Ding X, Foley J, Afshari C, Barrett J, Davis B . Loss of expression and altered localization of KAI1 and CD9 protein are associated with epithelial ovarian cancer progression. Gynecol Oncol. 2002; 86(1):69-78. DOI: 10.1006/gyno.2002.6729. View