RECK 是一种候选肿瘤抑制基因，被分离为在 KRAS 癌基因转化的细胞系中诱导平坦回复的基因。由于RECK敲除小鼠在子宫内死亡，因此它们不适合研究RECK对肿瘤形成的影响。在这项研究中，我们发现 RECK 表达减少的小鼠（RECK-Hypo 小鼠）自发性肺腺瘤的发病率增加。为了评估肿瘤细胞或宿主细胞表达的 RECK 对肿瘤生长的影响，我们从 C57BL/6 小鼠的肾脏建立了致瘤细胞系 (MKER)，并进行了同基因移植实验。我们的结果表明，当宿主细胞中 RECK 表达较低时，移植的 MKER 细胞生长得更快，并且更快地杀死动物。由于 RECK 是形成适当的原纤维蛋白纤维所必需的，而原纤维蛋白纤维可作为 TGFβ 家族细胞因子前体的组织储存库，因此我们评估了外周血中 TGFβ1 的水平。我们发现与野生型小鼠相比，RECK-Hypo 小鼠的 TGFβ1 显着增加。我们还发现，与对照小鼠相比，RECK-Hypo 小鼠脾细胞中 FOXP3 阳性调节性 T (Treg) 细胞的比例更高。此外，与对照小鼠相比，RECK-Hypo 小鼠肺部自发性造血肿瘤以及 MKER 移植后形成的肿瘤中 FOXP3 阳性细胞的数量显着更高。这些发现表明 RECK 介导的肿瘤抑制涉及非细胞自主机制，并且 TGFβ1 和 Treg 细胞在这种机制中的可能作用值得进一步研究。© 2024 作者。 《细胞生理学杂志》由 Wiley periodicals LLC 出版。

RECK is a candidate tumor suppressor gene isolated as a gene that induces flat reversion in a cell line transformed by the KRAS oncogene. Since RECK knockout mice die in utero, they are not suitable for studying the effects of RECK on tumor formation. In this study, we found an increased incidence of spontaneous pulmonary adenomas in mice with reduced RECK expression (RECK-Hypo mice). To evaluate the effects of RECK expressed by either tumor cells or host cells on tumor growth, we established a tumorigenic cell line (MKER) from the kidney of a C57BL/6 mouse and performed syngeneic transplantation experiments. Our results indicate that when RECK expression is low in host cells, transplanted MKER cells grow faster and kill the animal more rapidly. Since RECK is required for the formation of proper fibrillin fibers that serve as a tissue reservoir for precursors of TGFβ-family cytokines, we assessed the levels of TGFβ1 in the peripheral blood. We found a significant increase in TGFβ1 in RECK-Hypo mice compared to wild-type mice. We also found that the proportion of FOXP3-positive regulatory T (Treg) cells among splenocytes was higher in RECK-Hypo mice compared to the control mice. Furthermore, the number of FOXP3-positive cells in spontaneous hematopoietic neoplasms in the lungs as well as tumors that formed after MKER transplantation was significantly higher in RECK-Hypo mice compared to the control mice. These findings indicate that RECK-mediated tumor suppression involves a non-cell-autonomous mechanism and that possible roles of TGFβ1 and Treg cells in such a mechanism warrant further study.© 2024 The Author(s). Journal of Cellular Physiology published by Wiley Periodicals LLC.