FIBROBLAST CELL-INTERACTIONS WITH HUMAN-MELANOMA CELLS AFFECT TUMOR-CELL GROWTH AS A FUNCTION OF TUMOR PROGRESSION
FIBROBLAST CELL-INTERACTIONS WITH HUMAN-MELANOMA CELLS AFFECT TUMOR-CELL GROWTH AS A FUNCTION OF TUMOR PROGRESSION
复制标题
DOI：
10.1073/pnas.88.14.6028
复制
发表时间：
1991-07-01
影响因子：
11.1
通讯作者：
KERBEL, RS
中科院分区：
文献类型：
--
作者：
CORNIL, I;THEODORESCU, D;KERBEL, RS
从各种实验系统中已知，肿瘤细胞局部生长和转移的能力可受到相邻正常组织和细胞，特别是间充质来源的基质细胞如成纤维细胞的存在的影响。然而，这种正常细胞-肿瘤细胞相互作用对肿瘤行为的比较影响尚未从肿瘤进展的不同阶段的角度进行彻底研究。为了解决这个问题，我们评估了正常皮肤成纤维细胞对从肿瘤进展的不同阶段获得的人黑色素瘤细胞生长的影响。我们发现，在体外生长的大多数（5个中的4个）黑色素瘤细胞系衍生自早期放射状生长期或垂直生长期转移能力不足的原发性病变被抑制与正常皮肤成纤维细胞共培养，这表明负稳态生长控制仍然是从疾病的早期阶段的黑色素瘤细胞。另一方面，发现11个黑素瘤细胞系中有9个来自晚期有转移能力的垂直生长期原发性病变或来自远处转移瘤，在真皮成纤维细胞存在下持续刺激生长。获得的证据表明，这种区别性成纤维细胞影响是由可溶性抑制和刺激生长因子介导的。总之，这些结果表明，成纤维细胞衍生的信号可以对转移性肿瘤亚群与转移能力低下的肿瘤亚群具有相反的生长作用。这种对宿主组织环境因素的反应性的转化可能赋予少量的转移能力细胞生长优势，使它们能够逃避原发肿瘤部位和远处异位组织部位的局部生长限制。
It is known from a variety of experimental systems that the ability of tumor cells to grow locally and metastasize can be affected by the presence of adjacent normal tissues and cells, particularly mesenchymally derived stromal cells such as fibroblasts. However, the comparative influence of such normal cell-tumor cell interactions on tumor behavior has not been thoroughly investigated from the perspective of different stages of tumor progression. To address this question we assessed the influence of normal dermal fibroblasts on the growth of human melanoma cells obtained from different stages of tumor progression. We found that the in vitro growth of most (4 out of 5) melanoma cell lines derived from early-stage radial growth phase or vertical growth phase metastatically incompetent primary lesions is repressed by coculture with normal dermal fibroblasts, suggesting that negative homeostatic growth controls are still operative on melanoma cells from early stages of disease. On the other hand, 9 out of 11 melanoma cell lines derived from advanced metastatically competent vertical growth phase primary lesions, or from distant metastases, were found to be consistently stimulated to grow in the presence of dermal fibroblasts. Evidence was obtained to show that this discriminatory fibroblastic influence is mediated by soluble inhibitory and stimulatory growth factor(s). Taken together, these results indicate that fibroblast-derived signals can have antithetical growth effects on metastatic versus metastatically incompetent tumor subpopulations. This resultant conversion in responsiveness to host tissue environmental factors may confer upon small numbers of metastatically competent cells a growth advantage, allowing them to escape local growth constraints both in the primary tumor site and at distant ectopic tissue sites.