An embryo-specific expressing TGF-β family protein, growth-differentiation factor 3 (GDF3), augments progression of B16 melanoma.
An embryo-specific expressing TGF-β family protein, growth-differentiation factor 3 (GDF3), augments progression of B16 melanoma.
复制标题
DOI：
10.1186/1756-9966-29-135
复制
发表时间：
2010-10-15
期刊：
影响因子：
--
通讯作者：
Seya T
中科院分区：
文献类型：
--
作者：
Ehira N;Oshiumi H;Matsumoto M;Kondo T;Asaka M;Seya T
恶性肿瘤细胞通常表达与胚胎干细胞（ES）相同的胚胎抗原。胚胎抗原通常由胚胎干细胞特异性基因编码，其中一些基因与肿瘤发生和/或肿瘤进展有关。我们检测了小鼠B16黑色素瘤细胞系中ES细胞特异性基因的表达，以确定促进肿瘤发生的因素。我们发现内生生长分化因子3 （endogenous growth-differentiation factor 3, GDF3）在C57BL/6小鼠植入体B16肿瘤的进展过程中被诱导表达。B16 F10是一个具有高转移潜力的亚系，持续表达GDF3，而低转移的B16 F1表达GDF3水平相对降低。GDF3过表达促进同种小鼠植入黑色素瘤B16 F1和F10的生长。GDF3的异位表达伴随着CD24/CD44产生水平的增加。据报道，这种特征是黑色素瘤干细胞样细胞的特征。GDF3在胚胎癌、原发性睾丸生殖细胞瘤、精原细胞瘤和乳腺癌中均有表达。然而，GDF3在这些癌症中的作用仍未确定。过表达GDF3不影响小鼠肝癌高转移亚群G5或G1的生长，两者均不表达GDF3。由于gdf3驱动的CD24作为调节细胞增殖的内源性先天免疫配体的受体，因此CD24是恶性细胞转化中肿瘤发生的有效决定因素。最后，我们的结果支持GDF3能够诱导小鼠cd24诱导的黑色素瘤进展的观点。
Malignant tumor cells often express embryonic antigens which share the expression with embryonic stem (ES) cells. The embryonic antigens are usually encoded by ES cell-specific genes, a number of which are associated with tumorigenesis and/or tumor progression. We examined the expression of ES cell-specific genes in the mouse B16 melanoma cell line to identify the factors promoting tumorigenesis. We found that endogenous growth-differentiation factor 3 (GDF3) expression was induced in implant B16 tumor during tumor progression in syngenic C57BL/6 mice. B16 F10, a subline with a high metastatic potential, continuously expressed GDF3 while low metastatic B16 F1 expressed comparatively decreased levels of GDF3. Overexpression of GDF3 promoted growth of implanted melanoma B16 F1 and F10 in syngenic mice. Ectopic expression of GDF3 was accompanied by an increased level of production of CD24/CD44. Such a profile was reported to be characteristic of melanoma stem cell-like cells. GDF3 expression was observed in embryonal carcinomas, primary testicular germ cell tumors, seminomas and breast carcinomas. However, the role of GDF3 in these cancers remains undetermined. Overexpression of GDF3 did not affect the growth of mouse hepatoma high or low metastatic sublines G5 or G1, both of which do not express GDF3. Since GDF3-driven CD24 acts as a receptor for endogenous innate immune ligands that modulate cell proliferation, CD24 is an effective determinant of tumorigenesis in malignant cell transformation. Finally, our results support the view that GDF3 has the ability to induce progression of CD24-inducible melanoma in mice.