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Irradiation Reduces Interstitial Fluid Transport and Increases the Collagen Content in Tumors

¹ Department of Chemical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania;
² Departments of Radiation Oncology and
³ Cell Biology and Physiology, University of Pittsburgh, Pittsburgh, Pennsylvania;
⁴ Department of Radiation Medicine, Evanston Northwestern Healthcare, Evanston, Illinois;
⁵ Biological Engineering Division, Massachusetts Institute of Technology, Cambridge, Massachusetts; and
⁶ Department of Radiation Oncology, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts

ABSTRACT

Purpose: We have shown that the interstitial diffusion of large molecules is significantly hindered in tumors with high collagen levels. Because large therapeutic agents (e.g., monoclonal antibodies and viral vectors) will be combined with radiation or chemotherapy, it is significant to determine how cytotoxic therapies modify the transport and composition of the interstitial space in tumors. To test the hypothesis that radiation alters tumor interstitial transport, we measured tumor hydraulic conductivity (K) and hyaluronan and collagen type I levels after irradiation.

Experimental Design: K and the quantification of interstitial matrix components were determined in sections of s.c. implants of the human colon adenocarcinoma LS174T. K was measured on days 1 and 5 after 10 Gy of irradiation or on day 5 after 30 Gy of irradiation.

Results: Compared with control tumors, K decreased by approximately 12-fold after 10 or 30 Gy of irradiation on day 5. At 24 h after irradiation with 10 Gy, the decrease in K was not significant. Five days after 10 and 30 Gy of irradiation, the decrease in K was associated with significantly higher levels of collagen type I. The collagen type I content was not changed 24 h after irradiation with 10 Gy. Irradiation did not significantly increase hyaluronan levels in LS174T tumors.

Conclusions: After irradiation, the decrease in K and increase in collagen type I levels could significantly hinder the convective movement and diffusion of large therapeutic agents in tumors.

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