Differential permeability of lymphatic and blood vessels in determining the route of metastasis as demonstrated by indirect lymphography

Abstract

Indirect mammo-lymphography with serial radiograms was made on rats bearing three established rat mammary carcinomas (SMT-2A, TMT-50, MT-W9B), with the water-soluble contrast medium, Iotasul. In the lymphogenously metastasizing SMT-2A, fine lymphatic sprouts from the tumor were seen converging into an afferent lymph vessel that was extending toward a metastatic regional lymph node, in 15-30 min. For 45 min, the dye remained localized in the primary tumor with no other vascular structures or viscera visible until it emerged in the urinary bladder, indicating that Iotasul was absorbed slowly into the systemic circulation via lymphatics and diluted beyond recognition by lymph and blood, and then reconcentrated in urine. In contrast, in the hematogenously metastasizing TMT-50, Iotasul was rapidly diffused into the blood stream, revealing the inferior caval vein within 5 min, and by 15 min the heart, aorta, common carotid arteries, kidney and ureter were all clearly revealed. In the non-metastasizing MT-W9B host, several small vascular markings around the tumor were seen by 10 min and the outline of kidneys and urinary bladder in 15 min, suggesting that the dye was also absorbed through blood capillaries but somewhat slowly. Thus, the differential vascular permeability in rat mammary tumors revealed by Iotasul has not only helped to distinguish lymphatics from blood vessels, but also to correlate it with their metastatic potential.

Lymphatic endothelial cells support tumor growth in breast cancer

“…Lymphatic vessels (LV) in the tumor microenvironment are primarily considered as a route of tumor dissemination 17 . LV are leaky compared to blood vessels, because they are only sparsely covered with pericytes and smooth muscle cells 18 . Thus in certain types of cancers such as in breast cancer, metastasis occurs preferentially through the lymphatic vasculature compared to the blood vessel mediated spreading 19 20 .…”

Model of vascular desmoplastic multispecies tumor growth

“…Not surprisingly, studies found that peritumoral and intratumoral lymphatic microvessels are also disorganized and lack drainage function (Isaka et al, 2004; Padera et al, 2002). This structural irregularity might contribute to their susceptibility to invading malignant cells (Kim et al, 1988). …”