Metastatic colo-rectal cancer cells stimulate collagen production by fibroblasts.

In the metastatic cascade the interactions between tumor cells and the neighbouring extracellular matrix (ECM) or fibroblasts playa pivotal role. The aims of this study were to verify whether: 1. metastatic and nonmetastatic colorectal cancer (CRC) homogenates influence differently fibroblasts growth and collagen (PIlIP) production; and 2. sera from stage matched patients with CRC influence differently fibroblasts growth and PIlIP production in relation to disease progression after curative surgery. CRC specimens were obtained from 11 patients, 5 with and 6 without liver metastasis. The tumors were homogenized in PBS (1:20 w/v). Sera were obtained from 20 control subjects (CS), and from 57 patients with CRC, who were surgically treated and then followed up for a median period of 36 months. 28 CRC patients developed (group 2) and 29 did not developed (group I) a recurrent disease. Fibroblasts, obtained from saphena veins of healthy subjects, were plated (2000/well) in 96 well plates and cultured for one week in DMEM containing FCS 12.5%, added with 10% tumor homogenates or 10% heat inactivated patients' sera. The XTT assay (fibroblasts growth) and PIlIP levels in the supernatants were assessed after 1, 4 and 8 days of culture. Tumor homogenates did not modify fibroblasts' growth in relation to the presence or absence of metastases; PIlIP production after 8 days of culture was significantly induced by tumor homogenates obtained from metastatic (2.14::!:0.06 UlmL, mean::!:SD) than from non-metastatic disease (l.69::!:0.14 UlmL) (p<O.OI). Fibroblasts growth and PIlIP production significantly increases over time when conditioned with CS (Repeated measures anova: F=31.9, p<O.OOI and F= 13.9, p<O.OOI), group I (F=19.3, p<O.OOI and F=9.03, p<O.OI) or group 2 (F=20A, p<O.OOI and F=32.7, p<O.OOI) patients' sera. The percentage of PIlIP production after 8 days of culture over basal values was significantly higher in group 2 (l24::!: 16 %, meanz Slf) as compared to CS (111::!:9 %) or group I (l18::!:21 %) (F=3.3, p<0.05). In conclusion: CRC cells with a metastatic potential stimulate PIlIP production by fibroblasts; this ability seems related to the release of soluble mediators passing into the bloodstream; this secretory property of potentially metastatic colorectal cancer cells precedes the onset of clinically evident metastases and might be a prognostic indicator.