161 DEVELOPING COMPUTATIONAL METHODS TO VIEW DISTRIBUTIONS OF SECOND CANCER RISK USING MONTE CARLO AND VOXEL HUMAN PHANTOMS

Autor: R. Hugtenburg, W. Alsaleh
Rok vydání: 2012
Předmět:
Zdroj: Radiotherapy and Oncology. 102:S75
ISSN: 0167-8140
DOI: 10.1016/s0167-8140(12)70132-9
Popis: Purpose: Carcinoma-Associated Fibroblasts (CAFs) are major components of solid malignancies and play central roles in cancer sustainability. In this study we have investigated the invasive capacity and matrix remodelling properties of human lung CAFs after exposure to ablative doses of ionizing radiation (IR), corresponding to fractions delivered by stereotactic ablative radiotherapy (SART) for medically inoperable stage-I/II non-small-cell lung cancers. Methods: CAFs were isolated from lung tumor specimens from 15 donors. The migrative and invasive capacities of CAFs were determined after a sub-lethal single radiation dose of 18 Gy. To ascertain the mechanisms behind the altered invasive capacity of cells, the expression of matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs) were measured in the conditioned media several days postirradiation, along with the expression of cell surface integrins and the dynamics of focal contacts by vinculin-staining. Results: Exposure to 1x18 Gy resulted in premature cellular senescence and caused inhibition of the proliferative, migrative and invasive capacity in CAFs. IR promoted MMP-3 and inhibited MMP-1 appearance to some extent, but did not affect the expression of other major MMPs. Furthermore, surface expression of integrins α2, β1 and α5 was consistently enhanced, and a dramatic augmentation and redistribution of focal contacts was observed. Conclusions: Our data indicate that ablative doses of IR, which are increasingly offered by hypofractionated radiotherapy regimens, exert advantageous inhibitory effects on the proliferative, migratory and invasive capacity of lung CAFs. The reduced motility of irradiated CAFs might be a consequence of partial reduction in MMP-1 expression and stabilization of focal contacts via integrins.
Databáze: OpenAIRE
Externí odkaz: