BIOLOGY OF SOLID TUMOR GROWTH AND IMMUNE REJECTION

这项研究的目的是评估纤维蛋白的作用 肿瘤生长生物学中的沉积和周转，特别是 关于肿瘤基质形成。 在过去的一年里，我们完成了 关于纤维蛋白原内流和纤维蛋白定量的初步研究 在两种特征良好的豚鼠癌中的沉积和转换， 1号线和10号线胆管肿瘤。 早期免疫荧光研究 显示两个肿瘤中的纤维蛋白沉积（线1比线2大得多）。 10）。 雅阁纤维蛋白原（GPF） 在两个肿瘤中的累积量与血浆中的相当或超过血浆中的 纤维蛋白原水平。 然而，1号线肿瘤GPF含量是4倍， 10号线肿瘤和正常皮下组织的11至33倍。 聚集的GPF大部分以交联形式存在 （转氨）纤维蛋白。 因为纤维蛋白原最初流入 两种肿瘤的肿瘤和凝血是相同的， 在GPF积累中（第1行大于第10行），显然反映了 纤维蛋白溶解的差异。 其他研究关注的是 肿瘤相关促凝剂与肿瘤纤维蛋白沉积的关系。 几种肿瘤 促凝血活性已经在内源性和 外源性凝血途径，以及提供表面， 凝血酶原酶的产生，是常见凝血过程中的倒数第二步 这是一个重要的途径，也是凝血过程完成的关键。 然而，在这方面， 我们在过去一年的研究表明，肿瘤相关的促凝剂 可能没有我们之前想象的那么重要 我们发现 仅增加微血管通透性就足以诱导 几种正常组织中的等效血管外凝血。 的 结果表明，即使在 与正常结缔组织细胞相关的正常组织。 因此，微血管通透性的水平成为速率 在实体瘤的血管外凝固中的限制性步骤， 广泛的炎症反应 （一）

The goal of this research has been to evaluate the role of fibrin deposition and turnover in the biology of tumor growth, particularly with reference to tumor stroma formation. In the past year we have completed initial studies concerning the quantitation of fibrinogen influx and fibrin deposition and turnover in two well-characterized guinea pig carcinomas, line 1 and line 10 bile duct tumors. Earlier immunofluorescence studies revealed fibrin deposits in both tumors (line 1 much greater than line 10). In accord with these data, trace-labeled guinea pig fibrinogen (GPF) accumulated in both tumors in amounts that matched or exceeded plasma fibrinogen levels. However, line 1 tumor GPF content was four times that of line 10 tumors and 11 to 33 times that of normal subcutaneous tissue. The great bulk of accumulated GPF was in the form of cross linked (transglutaminated) fibrin. Because initial influx of fibrinogen into tumors and clotting were identical for both tumors, the large differences in GPF accumulation (line 1 greater than line 10) apparently reflect differences in fibrinolysis. Other studies have been concerned with the nature and importance of tumor-associated procoagulants to tumor fibrin deposition. Several tumor procoagulant activities have been identified in both the intrinsic and extrinsic coagulation pathways, as well as provision of a surface for prothrombinase generation, the penultimate step in the common coagulation pathway and one essential for clotting to proceed to completion. However, our studies in the past year have shown that tumor-associated procoagulants may be very much less important than had been thought earlier. We found that increased microvascular permeability alone is sufficient to induce equivalant extravascular coagulation in several normal tissues. The results indicate that saturating levels of procoagulant are present even in normal tissues in association with normal connective tissue cells. Therefore, the level of microvascular permeability becomes the rate limiting step in extravascular coagulation for solid tumors and also for a broad spectrum of inflammatory reactions. (A)