Abstract
The objective of this work was to introduce a tumor vessel classification scheme and to provide the first quantitative measurements of vessel branching patterns and the related vascular dimensions in a mammary carcinoma. Mammary adenocarcinoma R3230AC tumors, grown in the rat ovarian tissue-isolated tumor preparation, were infused with Batson's No. 17 polymer and maintained at an intravascular pressure of 50 mm Hg during polymerization. Maceration of the tumor in KOH allowed visualization of the vasculature. The vessel branching patterns, lengths, and diameters were measured in four tumors (4–5 g). A centrifugal ordering scheme was devised specifically to account for the unique features of tumor microvascular network topology.
The arterial networks revealed two types of branching patterns. One type of arteriolar network exhibited decreasing vessel diameters and lengths with increasing branch order. In a second type of network, the diameter and length of the vessels displayed fluctuations in both variables at higher generations. Avascular and poorly vascularized regions with sparse capillary supply were present in the tumors, but analysis of several capillary networks in vascularized regions revealed a nonplanar meshwork of interconnected vessels. The meshworks were composed of vessels with a mean segment length of 67 μm, a mean diameter of 10 μm, and a mean intercapillary distance of 49 μm. Capillary path lengths ranged from 0.5 to 1.5 mm. Thus, tumor capillary diameter was greater than that in most normal tissues and, in the regions where capillary networks existed, intercapillary spacing was in the normal range. In the venous network, diameters decreased from 650 to 20 μm for the first to ninth order venules. Venule length decreased from 5 to 0.5 mm for first to fourth order but was fairly uniform (<500 μm) for higher orders.
In conclusion, solid tumor vascular architecture, while exhibiting several features that are similar to those observed in normal tissues, has others that are not commonly seen in normal tissues. These features of the tumor microcirculation may lead to heterogeneous local hematocrits, oxygen tensions, and drug concentrations, thus reducing the efficacy of present day cancer therapies.
Supported by American Cancer Society Grants PF3551 (J. R. L.) and INI49B (T. C. S.) and National Cancer Institute Grant CA37239 (R. K. J.). Preliminary reports of this work were presented at the FASEB/Microcirculation Society Annual Meeting, New Orleans, LA, March 1989, at the Radiation Research Society Annual Meeting, Seattle, WA, March 1989, and at the American Institute of Chemical Engineers Meeting, San Francisco, CA, November 1989.