TUMOR-DERIVED CHEMOTACTIC FACTOR(S) FROM HUMAN OVARIAN-CARCINOMA - EVIDENCE FOR A ROLE IN THE REGULATION OF MACROPHAGE CONTENT OF NEOPLASTIC TISSUES

TUMOR-DERIVED CHEMOTACTIC FACTOR(S) FROM HUMAN OVARIAN-CARCINOMA - EVIDENCE FOR A ROLE IN THE REGULATION OF MACROPHAGE CONTENT OF NEOPLASTIC TISSUES
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DOI:
10.1002/ijc.2910360207
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发表时间:
1985-01-01
影响因子:
6.4
通讯作者:
MANTOVANI, A
MANTOVANI, A
中科院分区:
医学1区
文献类型:
--
作者:
BOTTAZZI, B;GHEZZI, P;MANTOVANI, A

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在盲孔趋化室中,检测来自体外维持24小时的新鲜解聚的人卵巢癌、来自原代卵巢癌培养物(培养4-6天)和建立的卵巢癌细胞系的上清液对血液单核细胞的趋化活性。肿瘤细胞培养上清液诱导外周血单核细胞迁移通过聚碳酸酯过滤器,不同肿瘤之间具有相当大的异质性。迁移的诱导仅发生在室的下部和上部隔室之间存在梯度的情况下。趋化活性的特点是从原发性卵巢癌培养的上清液。在无血清条件下产生趋化因子,其产生可被雌二醇抑制,但不被丝裂霉素C抑制。通过暴露于蛋白水解酶并在100 ℃下加热来破坏活性。但不受RNA酶、DNA酶、脂肪酶和暴露于极端pH值或在56 ℃加热的影响。C.在Sephadex G 75上分级分离后,活性在细胞色素C区域洗脱为单峰,对应于约12 kd的表观MW。在25个新鲜分解的肿瘤标本中评估巨噬细胞的百分比。卵巢癌的巨噬细胞含量不均匀,数值范围为4- 36%。一个显着的(r = 0.62; P = 0.00097),但远离绝对,相关性之间的趋化活性的培养上清液和肿瘤相关的巨噬细胞的百分比。肿瘤源性趋化因子可能是调节卵巢癌巨噬细胞含量的机制之一。
Supernatants from freshly disaggregated human ovarian carcinomas maintained in vitro for 24 h, from primary ovarian carcinoma cultures (4-6 days in culture) and established ovarian cancer cell lines were examined for chemotactic activity on blood monocytes in blind-well chemotaxis chambers. Tumor-cell culture supernatants induced migration of peripheral blood monocytes across polycarbonate filters with considerable heterogeneity among different tumors. Induction of migration occurred only in the presence of a gradient between the lower and upper compartments of the chamber. Chemotactic activity was characterized by means of supernatants from primary ovarian carcinoma cultures. Chemotactic factor(s) was (were) produced in serum-free conditions and the production was inhibited by emetine but not by mitomycin C. The activity was destroyed by exposure to proteolytic enzymes and heating at 100.degree. C but was unaffected by RNase, DNase, lipase and exposure to extreme pH values or heating at 56.degree. C. Upon fractionation on Sephadex G 75, the activity eluted as a single peak in the cytochrome C region, corresponding to an apparent MW of about 12 kd. The percentage of macrophages was assessed in 25 freshly disaggregated tumor specimens. Ovarian carcinomas were heterogeneous in their macrophage content with values ranging from 4-36%. A significant (r = 0.62; P = 0.00097), though far from absolute, correlation was found between chemotactic activity of culture supernatants and percentage of tumor-associated macrophages. Tumor-derived chemotactic factor(s) could be one of the mechanisms involved in the regulation of the macrophage content of human ovarian carcinomas.