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 Nacetylglucosaminyltransferase 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 crosslinking 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. INTRODUCTIONCD147/basigin/EMMPRIN, a cell surface transmembrane glycoprotein widely expressed on many cell types, appears at especially high levels on human tumor cells (Ellis et al., 1989;Muraoka et al., 1993;Polette et al., 1997). Elevated CD147 expression is correlated with tumor progression of gliomas (Sameshima et al., 2000a), hepatomas (Jiang et al., 2001), squamous cell carcinomas (Bordador et al., 2000), and melanomas (van den Oord et al., 1997; Kanekura et al., 2002). CD147/EMMPRIN on tumor cells stimulates production of multiple matrix metalloproteinases (MMPs) by tumor stromal cells, which is the basis of the name EMMPRIN (extracellular matrix metalloproteinase inducer) (Ellis et al., 1989;Kataoka et al., 1993). Tumor cell CD147 can stimulate stromal fibroblast production of interstitial collagenase (MMP-1), gelatinase A (MMP-2), and stromelysin (MMP-3) (Ellis et al., 1989;Kataoka et al., 1993;Sameshima et al., 2000b;Li et al., 2001;Suzuki et al., 2004). Similarly, recombinant purified or soluble secreted EMMPRIN glycoprotein stimulates fibroblasts to produce MMP-1, MMP-2, and MMP-3 (Guo et al., 1997;Li et al., 2001;Sun and Hemler, 2001;Taylor et al., 2002), and tumor-derived ...

Background-We prospectively assessed the incidence, risk factors, and costs associated with wound complications and lymphedema in melanoma patients undergoing inguinal lymph node dissection (ILND).

TheIt is well established that ligand binding and cell-surface clustering of integrins can lead to the assembly of large multicomponent intracellular signaling complexes (1-4). More recently, integrins have also been found to associate with other cell-surface molecules. For example, the CD47/IAP molecule associates with integrin ␣ V ␤ 3 (5, 6), and glycosylphosphatidylinositol-linked receptors such as CD87/uPAR, CD16b/ Fc␥RIIIB, and CD14 show functionally relevant interactions with ␤ 1 (7) and ␤ 2 (8, 9) integrins. In addition, proteins from the tetraspan or transmembrane-4 superfamily (TM4SF), 1 including CD9, CD53, CD63, CD81, and CD82, interact with several integrins, including ␣

To escape after taking a blood meal, a mosquito must exert forces sufficiently high to take off when carrying a load roughly equal to its body weight, while simultaneously avoiding detection by minimizing tactile signals exerted on the host's skin. We studied this trade-off between escape speed and stealth in the malaria mosquito Anopheles coluzzii using 3D motion analysis of high-speed stereoscopic videos of mosquito take-offs and aerodynamic modeling. We found that during the push-off phase, mosquitoes enhanced take-off speed using aerodynamic forces generated by the beating wings in addition to leg-based push-off forces, whereby wing forces contributed 61% of the total push-off force. Exchanging legderived push-off forces for wing-derived aerodynamic forces allows the animal to reduce peak force production on the host's skin. By slowly extending their long legs throughout the push-off, mosquitoes spread push-off forces over a longer time window than insects with short legs, thereby further reducing peak leg forces. Using this specialized take-off behavior, mosquitoes are capable of reaching take-off speeds comparable to those of similarly sized fruit flies, but with weight-normalized peak leg forces that were only 27% of those of the fruit flies. By limiting peak leg forces, mosquitoes possibly reduce the chance of being detected by the host. The resulting combination of high take-off speed and low tactile signals on the host might help increase the mosquito's success in escaping from blood-hosts, which consequently also increases the chance of transmitting vector-borne diseases, such as malaria, to future hosts.