Evidence of porcine and human endothelium activation by cancer-associated carbohydrates expressed on glycoproteins and tumour cells.
It is well established that after metastatic cancer cells escape the primary tumour and enter the circulation, their interactions with microvascular endothelium of a target organ constitute an essential rate-limiting step in haematogenous cancer metastasis. However, the physiological and biochemical processes supporting neoplastic cell arrest and retention in the microcirculation are still poorly understood. In this study, we present experimental evidence that microvascular endothelium of metastasis-prone tissues undergoes activation in response to desialylated cancer-associated carbohydrate structures such as Thomsen-Friedenreich (TF) antigen (Galbeta1-3GalNAc) expressed on circulating glycoproteins and neoplastic cells. The metastasis-associated endothelium activation, manifested by marked increase in endothelial cell surface galectin-3 expression, causes gradual decrease in cancer cell velocities (from 72 x 10(2)+/- 33 x 10(2) microm s-1 to 7.6 x 10(2)+/- 1.9 x 10(2) microm s-1, mean +/-s.d.) accompanied by a corresponding increase in the percentage of rolling cells (from 3.3%+/- 1.2% to 24.3%+/- 3.6%, mean +/-s.d.), and results in human breast and prostate carcinoma cell arrest and retention in the microvasculature. This process, which could be of high importance in haematogenous cancer metastasis, was inhibited efficiently by an anti-TF antigen function-blocking antibody. Carbohydrate-mediated endothelial activation could be a process of physiological significance as it probably occurs in the interactions between a variety of circulating constituents and the vessel wall.
Glinskii
Olga V
OV
Medical Pharmacology and Physiology Biomedical Sciences Biochemistry, University of Missouri, Columbia, MO 65212, USA. glinskiivl@missouri.edu
Turk
James R
JR
Pienta
Kenneth J
KJ
Huxley
Virginia H
VH
Glinsky
Vladislav V
VV
D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000378:metabolism*; D001212:Asialoglycoproteins / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000556:secondary; D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005260:Female; D060748:Fetuins; D037502:Galectin 3 / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008833:Microcirculation / Q000502:physiology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000556:secondary; D013552:Swine; D000509:alpha-Fetoproteins / Q000378:metabolism
D015295:Antigens, Tumor-Associated, Carbohydrate; D001212:Asialoglycoproteins; D060748:Fetuins; D037502:Galectin 3; D006023:Glycoproteins; D000509:alpha-Fetoproteins; C017029:asialofetuin; C016467:Thomsen-Friedenreich antigen