Site-specific epithelial-mesenchymal interactions in digestive neuroendocrine tumors - An experimental in vivo and in vitro study

Little is known about the functional interactions between digestive neuroen docrine tumor cells and their stromal microenvironment, The focus of our st udy is whether mesenchymal cells modulate peptide expression, cell prolifer ation, and invasiveness in digestive neuroendocrine tumor cells. We designe d an experimental in vivo and in vitro study using the mouse enteroendocrin e cell line STC-1. In vivo, STC-1 cells were injected subcutaneously in 18 immunosuppressed newborn rats. At day 21, all animals presented poorly diff erentiated neuroendocrine tumors with lung metastases, Subcutaneous tumors were usually limited by a capsule containing basement membrane components a nd myofibroblasts that presented a low mitotic index. Lung tumors were devo id of capsule and poor in myofibroblasts, and their mitotic index was high. The profile of peptide expression in STC-1 tumors was different from that of cultured STC-1 cells. In vitro, STC-1 cells were cultured with fibroblas ts of different origins, including dermis, lung, digestive tract, and liver . Based on their origin, myofibroblasts differentially modulated hormone sy nthesis, proliferation, spreading, and adhesion of STC-1 cells. In conclusi on, our results show that site-specific functional interactions between mes enchymal and neuroendocrine cells may contribute to modulating the behavior of digestive neuroendocrine tumors, depending on their growth site.