Relations of TGF-beta1 with HIF-1 alpha, GLUT-1 and longer survival of colorectal cancer patients.
OBJECTIVE
During colorectal carcinogenesis, transforming growth factor beta 1 (TGF-beta1) undergoes a functional change from suppression of cancer cell proliferation to inhibition of T cell mediated anti-cancer immunity. We aimed to evaluate relations among TGF-beta1 and cancer cell survival factors hypoxia inducible factor-1 alpha (HIF-1 alpha) and glucose transporter 1 (GLUT-1) by immunohistochemistry in 108 colorectal cancers.


RESULTS
TGF-beta1 was detected in 87% (94/108), HIF-1 alpha in 85% (92/108), and GLUT-1 in 65% (70/108) of colorectal cancers. Not only did TGF-beta1 accumulate in cytoplasm of cancer cells but also there was strong immunoreactivity to TGF-beta1 in adjacent inflammatory cells. GLUT-1 was visualised in a membranous fashion while HIF-1 was expressed in a paranuclear pattern and occasionally in nuclei of malignant cells. Cancer immunoreactivities to TGF-beta1 correlated with HIF-1 alpha (p < 0.001, r = 0.516) and GLUT-1 (p < [corrected] 0.001, r = 0.355) in general and subgroups of different clinicopathological traits. TGF-beta1 expressions of inflammatory infiltrates correlated with longer patient survival (p = 0.05, r = 0.449) and immunoreactivities to HIF-1 alpha of cancer cells (p = 0.008, r = 0.254) particularly in node positive and deeply invading cancers but failed to associate significantly with GLUT-1.


CONCLUSIONS
HIF-1 alpha and GLUT-1 could cooperate with TGF-beta1, and TGF-beta1 might mediate cross-talk between the inflammatory environment and tumour with a favourable impact on patient survival.
Sulkowska
Mariola
M
Department of General Pathomorphology, Medical University of Bialystok, Bialystok, Poland.
Wincewicz
Andrzej
A
Sulkowski
Stanislaw
S
Koda
Mariusz
M
Kanczuga-Koda
Luiza
L
D014408:Biomarkers, Tumor / Q000032:analysis; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality*; D051272:Glucose Transporter Type 1 / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007150:Immunohistochemistry; D020239:Receptor Cross-Talk / Q000502:physiology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D014408:Biomarkers, Tumor; D051272:Glucose Transporter Type 1; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D053773:Transforming Growth Factor beta1