Haslam S Z
Cancer Res. 1986 Jan;46(1):310-6.
Estrogen-dependent stimulation of progesterone receptor (PgR) concentration or cell proliferation of normal mammary epithelial cells in vitro has been shown to be associated with the presence of mammary fibroblasts. To investigate further the nature of fibroblast influence on epithelial cells, Percoll-purified epithelial cells from collagenase-dissociated mammary glands of mid-pregnant BALB/c mice were co-cultured with mammary fibroblasts that were either untreated, irradiated, or glutaraldehyde-killed or with fibroblast-conditioned medium. Epithelial cells were then assayed for either estrogen-dependent stimulation of PgR by measuring specific [3H]R5020 binding or for estrogen-dependent stimulation of DNA synthesis by [3H]thymidine autoradiography. The results demonstrate that stimulation of PgR does not require the presence of live fibroblasts; either glutaraldehyde-killed fibroblasts or conditioned medium was effective. Pretreatment of culture dishes with type I collagen was equally effective, indicating that fibroblasts may promote the PgR response via a substratum effect. In distinct contrast, estrogen-dependent stimulation of DNA synthesis occurred only when live fibroblasts were present in high numbers and/or in direct contact with epithelial cells. Furthermore, under these latter conditions, epithelial cells also promoted estrogen-dependent stimulation of fibroblast DNA synthesis. Differences in both epithelial and fibroblast cell morphologies were also observed under co-culture conditions, which suggested that cell-cell communication or another interactive phenomenon takes place and is bidirectional. Thus there appear to be at least two different mechanisms by which fibroblasts can influence two specific responses of epithelial cells to estrogen. The present results demonstrate that the specific nature of epithelial-stromal interactions can determine and modulate epithelial cell responses to estrogen and may reflect in vivo regulatory processes affecting normal and neoplastic mammary cells.
体外雌激素依赖性刺激正常乳腺上皮细胞的孕激素受体（PgR）浓度或细胞增殖已被证明与乳腺成纤维细胞的存在有关。为了进一步研究成纤维细胞对上皮细胞影响的本质，将来自妊娠中期BALB/c小鼠胶原酶解离乳腺的Percoll纯化上皮细胞与未处理、照射、戊二醛杀死的乳腺成纤维细胞或成纤维细胞条件培养基共培养。然后通过测量特异性[3H]R5020结合来检测上皮细胞对雌激素依赖性PgR刺激，或通过[3H]胸腺嘧啶核苷放射自显影来检测雌激素依赖性DNA合成刺激。结果表明，PgR的刺激不需要活的成纤维细胞存在；戊二醛杀死的成纤维细胞或条件培养基均有效。用I型胶原预处理培养皿同样有效，表明成纤维细胞可能通过基质效应促进PgR反应。截然不同的是，仅当大量活的成纤维细胞存在和/或与上皮细胞直接接触时，才会发生雌激素依赖性DNA合成刺激。此外，在这些后一种条件下，上皮细胞也促进了雌激素依赖性成纤维细胞DNA合成刺激。在共培养条件下还观察到上皮细胞和成纤维细胞形态的差异，这表明细胞间通讯或另一种相互作用现象发生且是双向的。因此，成纤维细胞似乎至少有两种不同机制可影响上皮细胞对雌激素的两种特定反应。目前的结果表明，上皮-基质相互作用的具体性质可以决定和调节上皮细胞对雌激素的反应，并可能反映影响正常和肿瘤性乳腺细胞的体内调节过程。
