Tumor cell arrest in the microcirculation: lack of evidence for a leukocyte-like rolling adhesive interaction with vascular endothelium in vivo.
Hematogenous spread of tumor cells and metastasis formation in secondary organs are insidious aspects of cancer. In the present intravital microscopic study in the rabbit mesentery, we examined the in vivo flow behavior of six human tumor cell lines of different histological origin. The tumor cells and human neutrophils were injected locally into a side branch of the superior mesenteric artery upstream of the observed microvascular area in the mesentery. None of the tumor cells behaved similar to the leukocytes of which a substantial fraction rolled along the endothelium of small venules. Thus, the tumor cells passed the same venular segments without interacting with the endothelial lining. Yet, three of the tumor cell lines (HT-29, DLD-1, and HCT-8) were strongly positive for the oligosaccharides Lewis(x), sialyl-Lewis(x), and sialyl-Lewis(a) which are recognized by the endothelial selectins that mediate leukocyte rolling. On the other hand, some tumor cells were trapped in the smallest vessels and remained so throughout the experimental period, apparently due to a discrepancy in size between tumor cells and microvessel lumen. Taken together, our in vivo findings suggest that initial microvascular arrest of metastasizing tumor cells is dependent primarily on mechanical factors rather than on receptor-mediated leukocyte-like adhesive interactions.
Thorlacius
H
H
Department of Physiology & Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Prieto
J
J
Raud
J
J
Gautam
N
N
Patarroyo
M
M
Hedqvist
P
P
Lindbom
L
L
D000818:Animals; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D019040:E-Selectin / Q000096:biosynthesis; D005260:Female; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D019012:Integrin beta1 / Q000096:biosynthesis; D008643:Mesentery / Q000098:blood supply; D008833:Microcirculation / Q000166:cytology*; D009360:Neoplastic Cells, Circulating / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009504:Neutrophils / Q000502:physiology; D010581:Peyer's Patches / Q000098:blood supply; D011817:Rabbits; D014407:Tumor Cells, Cultured
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D018960:Hyaluronan Receptors; D019012:Integrin beta1