Westerlund A, Hujanen E, Puistola U, Turpeenniemi-Hujanen T
Department of Oncology and Radiotherapy, University Hospital of Oulu, Finland.
Gynecol Oncol. 1997 Oct;67(1):76-82. doi: 10.1006/gyno.1997.4808.
The host-tumor interactions and tumor stroma may participate in the regulation of invasive behavior of tumor cells. In order to better understand the human ovarian cancer invasion we explored the possibility that normal fibroblasts could participate in the control of the spread of human ovarian cancer.
A 3.5-fold increase (from 2.83 +/- 0.97 to 10.2 +/- 3.43%) in human ovarian cancer cell (Ovcar-3) invasion through a reconstituted basement membrane was noted when normal fibroblasts (CRL 1295) were added to the invasion chambers in conjunction with tumor cells. Conditioned medium from either fibroblasts or Ovcar-3 also enhanced the in vitro invasion of Ovcar-3 by 2- to 2.5-fold (from 2.83 +/- 0.97 to 5.71 +/- 3.5 and to 7.15 +/- 1.2%, respectively) compared to nonstimulated control cells. Zymographic analysis and assays of mRNA for the 72-kDa matrix metalloproteinase (MMP-2) showed that Ovcar-3 cells alone produced very low levels of MMP-2; the expression of this gelatinase was detectable in zymography only with stimulation by incubation of these cells with conditioned media from either fibroblasts or ovarian cancer cells themselves. Interestingly, MMP-2 activity was increased also in fibroblasts when using either ovarian cancer cell-conditioned (to 178 +/- 67%) or fibroblast-conditioned medium (to 215 +/- 61%) and the gene expression for MMP-2 was similarly increased in both fibroblasts and Ovcar-3 cells when using either fibroblast-conditioned medium or ovarian cancer cell-conditioned medium from 1.00 +/- 0.25 to 2.20 +/- 0.50 and 1.86 +/- 0.10 in fibroblasts and from 1.00 +/- 0.26 to 1.60 +/- 0.34 and 2.15 +/- 0.30 in Ovcar-3 cells, respectively.
These results show that interplay between tumor cells and normal cells in the control of invasion and secretion of proteolytic enzymes may involve not only paracrine but also autocrine elements. Thus, such interactions are possible and may play an important role in the spread of cancer.
宿主与肿瘤的相互作用以及肿瘤基质可能参与肿瘤细胞侵袭行为的调控。为了更好地理解人类卵巢癌的侵袭过程，我们探讨了正常成纤维细胞是否能够参与控制人类卵巢癌扩散的可能性。
当将正常成纤维细胞（CRL 1295）与肿瘤细胞一起加入侵袭小室时，人类卵巢癌细胞（Ovcar-3）通过重组基底膜的侵袭能力增加了3.5倍（从2.83±0.97%增至10.2±3.43%）。与未受刺激的对照细胞相比，来自成纤维细胞或Ovcar-3的条件培养基也使Ovcar-3的体外侵袭能力增强了2至2.5倍（分别从2.83±0.97%增至5.71±3.5%和7.15±1.2%）。对72 kDa基质金属蛋白酶（MMP-2）进行的酶谱分析和mRNA检测显示，单独的Ovcar-3细胞产生的MMP-2水平非常低；只有在用来自成纤维细胞或卵巢癌细胞自身的条件培养基孵育刺激这些细胞后，才能在酶谱分析中检测到这种明胶酶的表达。有趣的是，当使用卵巢癌细胞条件培养基（增至178±67%）或成纤维细胞条件培养基（增至215±61%）时，成纤维细胞中的MMP-2活性也会增加；当使用成纤维细胞条件培养基或卵巢癌细胞条件培养基时，成纤维细胞和Ovcar-3细胞中MMP-2的基因表达也会类似地增加，成纤维细胞中从1.00±0.25增至2.20±0.50，Ovcar-3细胞中从1.00±0.26增至1.60±0.34和2.15±0.30。
这些结果表明，肿瘤细胞与正常细胞在侵袭控制和蛋白水解酶分泌方面的相互作用可能不仅涉及旁分泌，还涉及自分泌成分。因此，这种相互作用是可能的，并且可能在癌症扩散中发挥重要作用。
