![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 15, Issue 9, 4043-4050, September 2004
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dana-Farber Cancer Institute and Department of Pathology, Harvard Medical School, Boston, MA 02115
Submitted May 14, 2004;
Revised June 2, 2004;
Accepted June 7, 2004
Monitoring Editor: Reid Gilmore
Cell surface CD147 shows remarkable variations in size (31-65 kDa) because of heterogeneous N-glycosylation, with the most highly glycosylated forms functioning to induce matrix metalloproteinase (MMP) production. Here we show that all three CD147 N-glycosylation sites make similar contributions to both high and low glycoforms (HG- and LG-CD147). L-Phytohemagglutinin lectin binding and swainsonine inhibition experiments indicated that HG-CD147 contains N-acetylglucosaminyltransferase V-catalyzed, 
1,6-branched, polylactosamine-type sugars, which account for its excess size. Therefore, CD147, which is itself elevated on invasive tumor cells, may make a major contribution to the abundance of 1,6-branched polylactosamine sugars that appear on invasive tumor cells. It was shown previously that caveolin-1 associates with CD147, thus inhibiting CD147 self-aggregation and MMP induction; now we show that caveolin-1 associates with LG-CD147 and restricts the biosynthetic conversion of LG-CD147 to HG-CD147. In addition, HG-CD147 (but not LG-CD147) was preferentially captured as a multimer after treatment of cells with a homobifunctional cross-linking agent and was exclusively recognized by monoclonal antibody AAA6, a reagent that selectively recognizes self-associated CD147 and inhibits CD147-mediated MMP induction. In conclusion, we have 1) determined the biochemical basis for the unusual size variation in CD147, 2) established that CD147 is a major carrier of 1,6-branched polylactosamine sugars on tumor cells, and 3) determined that caveolin-1 can inhibit the conversion of LG-CD147 to HG-CD147. Because it is HG-CD147 that self-aggregates and stimulates MMP induction, we now have a mechanism to explain how caveolin-1 inhibits these processes. These results help explain the previously established tumor suppressor functions of caveolin-1.
Abbreviations used: Asn, asparagine; endo H, endoglycosidase H; GFP, green fluorescent protein; GnT, N-acetylglucosaminyltransferase; HUVEC, human umbilical vein endothelial cells; MCT, monocarboxylate transporter; MMP, matrix metalloproteinase; HG, highly glycosylated; LG, less glycosylated; L-PHA, L-phytohemagglutinin.
* Corresponding author. E-mail address: martin_hemler{at}dfci.harvard.edu.
This article has been cited by other articles:
|
|
 |
|
  K. S. Vetrivel, X. Zhang, X. Meckler, H. Cheng, S. Lee, P. Gong, K. O. Lopes, Y. Chen, N. Iwata, K.-J. Yin, et al. Evidence That CD147 Modulation of {beta}-Amyloid (A{beta}) Levels Is Mediated by Extracellular Degradation of Secreted A{beta} J. Biol. Chem., July 11, 2008; 283(28): 19489 - 19498. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Jansen, M. Pantaleon, and P. L Kaye Characterization and Regulation of Monocarboxylate Cotransporters Slc16a7 and Slc16a3 in Preimplantation Mouse Embryos Biol Reprod, July 1, 2008; 79(1): 84 - 92. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Belton Jr., L. Chen, F. S. Mesquita, and R. A. Nowak Basigin-2 Is a Cell Surface Receptor for Soluble Basigin Ligand J. Biol. Chem., June 27, 2008; 283(26): 17805 - 17814. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Morikawa, N. Ohara, Q. Xu, K. Nakabayashi, D. A. DeManno, K. Chwalisz, S. Yoshida, and T. Maruo Selective progesterone receptor modulator asoprisnil down-regulates collagen synthesis in cultured human uterine leiomyoma cells through up-regulating extracellular matrix metalloproteinase inducer Hum. Reprod., April 1, 2008; 23(4): 944 - 951. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Xu, N. Ohara, J. Liu, M. Amano, R. Sitruk-Ware, S. Yoshida, and T. Maruo Progesterone receptor modulator CDB-2914 induces extracellular matrix metalloproteinase inducer in cultured human uterine leiomyoma cells Mol. Hum. Reprod., March 1, 2008; 14(3): 181 - 191. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Odajima, T. Betsuyaku, Y. Nasuhara, and M. Nishimura Loss of Caveolin-1 in Bronchiolization in Lung Fibrosis J. Histochem. Cytochem., September 1, 2007; 55(9): 899 - 909. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Gallagher, J. J. Castorino, D. Wang, and N. J. Philp Monocarboxylate Transporter 4 Regulates Maturation and Trafficking of CD147 to the Plasma Membrane in the Metastatic Breast Cancer Cell Line MDA-MB-231 Cancer Res., May 1, 2007; 67(9): 4182 - 4189. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Schneiderhan, F. Diaz, M. Fundel, S. Zhou, M. Siech, C. Hasel, P. Moller, J. E. Gschwend, T. Seufferlein, T. Gress, et al. Pancreatic stellate cells are an important source of MMP-2 in human pancreatic cancer and accelerate tumor progression in a murine xenograft model and CAM assay J. Cell Sci., February 1, 2007; 120(3): 512 - 519. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. H. Yang, O. V. Kovalenko, T. V. Kolesnikova, M. M. Andzelm, E. Rubinstein, J. L. Strominger, and M. E. Hemler Contrasting Effects of EWI Proteins, Integrins, and Protein Palmitoylation on Cell Surface CD9 Organization J. Biol. Chem., May 5, 2006; 281(18): 12976 - 12985. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Xu and M. E. Hemler Metabolic Activation-related CD147-CD98 Complex Mol. Cell. Proteomics, August 1, 2005; 4(8): 1061 - 1071. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. E. Gabison, S. Mourah, E. Steinfels, L. Yan, T. Hoang-Xuan, M. A. Watsky, B. De Wever, F. Calvo, A. Mauviel, and S. Menashi Differential Expression of Extracellular Matrix Metalloproteinase Inducer (CD147) in Normal and Ulcerated Corneas: Role in Epithelio-Stromal Interactions and Matrix Metalloproteinase Induction Am. J. Pathol., January 1, 2005; 166(1): 209 - 219. [Abstract] [Full Text] [PDF]
|
|
