Studies on prediction and inhibition for metastasis from carcinomas of the digestive tract

我们建立了体外定量分析方法（侵袭性MTT法），用于研究消化道肿瘤细胞的侵袭潜力和转移行为。对基底膜的侵袭潜能用侵袭百分率来估计，即在细胞腔内穿透基底膜的种子细胞的发生率（入侵细胞与种子细胞的百分率）。肝转移瘤的侵袭率显著高于无转移瘤（p<0.001），但与IV型胶原酶活性、细胞粘附能力、趋化性和增殖能力均无相关性。IV型胶原酶活性在肝转移患者中明显升高，提示其对加速肝转移具有重要作用。通过对906例消化道癌患者的临床病理参数进行单因素分析，了解其对肝脏转移的预测能力，发现血管浸润和淋巴结转移是预测肝转移的重要参数。使用这些参数进行预测，其特异性大于90%，敏感性小于20%。然而，通过从906名患者中获得的30个肿瘤移植到裸鼠中来测量侵袭率。其预测特异性为90%，敏感性为70%。利用侵袭性MTT试验评估基底膜的侵袭性，似乎是预测消化道癌肝转移的有效方法。

We have established the method of in vitro quantitative assay (invasion MTT assay) for studying invasive potentiality and metastatic behavior of the cancer cells using carcinomas of the digestive tract. The invasive potentiality to the basement membrane was estimated as percent invasion, that is the occurrence of the seeded cells in the cell chamber which penetrate through the basement membrane (percentage of the invaded cells to the seeded cells). The percent invasion values of tumors with liver metastasis were significantly higher than those of tumors without metastasis (p<0.001), although, it did not correlate with both type IV collagenase activity and cell capability of the adhesion, chemotaxis, and proliferation. The type IV collagenase activity was significantly higher in patients with liver metastasis, suggesting it has an important role to accelerate the liver metastasis.Clinicopathological parameters in 906 patients with carcinomas of the digestive tract were studied to know prediction capability for the liver metastasis using univariate analysis, resulting that vessel invasion and lymph node metastasis were the significant parameters. Using those parameters for the prediction, its specificity was more than 90% but sensitivity was less than 20%. Whereas, the percent invasion was measured using 30 tumors xenografted in nude mice obtained from the 906 patients. Its specificity for the prediction was 90% and sensitivity was 70%. An assessment of invasive potentiality to the basement membrane using the invasion MTT assay seemed to be useful method for predicting the liver metastasis form carcinomas of the digestive tract.