Glucose-transporter-type-I-gene amplification correlates with Sialyl-Lewis-X synthesis and proliferation in lung cancer

Abstract

Increased glucose transport is a common characteristic of most tumors. To examine the role of elevated glucose uptake in lung cancer, we performed PCR amplification of 2 facilitative glucose transporter genes (GLUT1 and GLUT3) and immunohistochemical staining for GLUT1, proliferating cell nuclear antigen (PCNA), and sialyl Lewis 3 (sLe x ) on tumor specimens from 327 patients with lung cancer who underwent surgical resection from 1980 to 1993. To evaluate the relationship between GLUT, a-2,3-sialyltransferase (ST), and a-1,3-fucosyltransferase (Fuc-T) genes, PCR amplification of the ST3N and Fuc-TVII also was performed. Amplification of GLUT1 was significantly greater than that of GLUT3. GLUT1 and GLUT3 amplification correlated with PCNA staining (p F 0.01). In addition, GLUT1 amplification correlated with the grading of sLe x staining as well as with the grading of GLUT1 staining (p F .03, p F 0.01). GLUT1 was co-amplified with ST3N and Fuc-TVII genes, which are involved in the synthesis of sLe x (p F 0.01). The survival of patients whose tumors showed GLUT1 amplification was significantly shorter than that of patients whose tumors did not (p F 0.01). In a multivariate analysis of survival, GLUT1 remained a statistically significant prognostic factor. Our results suggest that GLUT1 amplification may participate in sLe x synthesis as well as in proliferation, and may be of prognostic value in lung cancer. Int.

Hypoxia induces adhesion molecules on cancer cells: A missing link between Warburg effect and induction of selectin-ligand carbohydrates

“…This result is supported also by a recent finding that disruption of the gene for a major galactosyltransferase results in a remarkable reduction of selectin-ligand expression in mice (47). Although the exact mechanism of the relationship between GLUT1 induction and sialyl Lewis x͞a is not clear, the good correlation of GLUT1 expression and sialyl Lewis x expression in clinical samples is known (12). Interestingly, GLUT1 encodes the major cellular transporter for not only glucose but also galactose.…”

“…Increased expression of UDP-galactose transporter gene (UGT1) in cancers was also suggested to be involved in the induction of these selectin ligands, because the introduction of the gene for UDP-galactose transporter conferred the induction of sialyl Lewis a and sialyl Lewis x expression on cultured cancer cells (8). Other investigators have suggested a role for fucosyltransferase VII (9)(10)(11) and even the involvement of another sugar transporter, GLUT1, for induction of sialyl Lewis x in cancers (12). However, the exact mechanism underlying this transcriptional induction has remained uncharacterized.…”

Molecular and cellular regulation of glucose transporter (GLUT) proteins in cancer

“…GLUT1 expression in tumors also correlates with the survival of patients. In lung, colorectal, ovarian, laryngeal, and breast carcinomas, high levels of GLUT1 or GLUT3 in the tumors were significant indicators of decreased survival (Baer et al, 1997;Ogawa et al, 1997;Younes et al, 1997;Haber et al, 1998;Cantuaria et al, 2001;Kang et al, 2002). GLUT1 staining has also been identified in 25% of hyperplastic breast tissue and 25% of histologically normal breast tissue adjacent to tumors (Alo et al, 2001).…”

Inhibition of MT-450 rat mammary tumour growth by antibodies recognising subtypes of blood group antigen B

“…Upregulation of fucosyltransferase activity and subsequent fucosylation of carbohydrate precursors is correlated with tumour progression and poor prognosis (Holmes, 1990;Sun et al, 1995;Ogawa et al, 1996). Furthermore, experimental modulation of a(1,2)fucosyltransferase activity can change the metastasizing properties of tumour cells (Labarriere et al, 1994;Goupille et al, 1997).…”