Department of Biology, Temple University College of Science and Technology, PA, USA.
Department of Pathology and Laboratory Medicine, Temple University School of Medicine, PA, USA.
Exp Mol Pathol. 2022 Apr;125:104751. doi: 10.1016/j.yexmp.2022.104751. Epub 2022 Feb 2.
We have identified the novel protein GASP-1 (G protein coupled receptor-associated sorting protein 1) that appears to be a universal cancer marker and the expression of which in tumor tissue and patient sera is predictive of cancer severity (Tuszynski et al. 2011; Zheng et al. 2012; Zheng 2013; Chang and Tuszynski, 2020). In preliminary results we discovered that a GASP-1 antibody inhibited the growth of the triple negative breast cancer cell line MDA-MB-231 and transient reduction of GASP-1 in these cells decreased their proliferation. To further substantiate these results, we over and under-expressed GASP-1 in stable clones of MDA-MB-231 cells and evaluated their growth and invasive activities. Cells under-expressing GASP-1 failed to grow after 4 days in culture and eventually died. In contrast GASP-1 expressing cells grew exponentially. Similarly, GASP-1 under-expressing cells formed 30% fewer colonies in soft agar as compared to controls and whereas GASP-1 over-expressing cells formed 2-fold more colonies than controls. In tumor cell invasion assays GASP-1 over-expressing cells were over 10-fold more invasive than controls whereas GASP-1 under-expressing cells were over 10-fold less invasive than controls. In IHC staining studies of breast cancer cells, we found that the overexpressed GASP-1 appear in granules of different sizes that are directly correlated with cancer invasiveness. Our results strongly indicate that GASP-1 promotes proliferation and invasion of the triple negative breast cancer cell line MDA-MB-231 and targeting GASP-1 for treatment of breast cancer is indicated.
我们已经确定了一种新型蛋白 GASP-1(G 蛋白偶联受体相关分拣蛋白 1),它似乎是一种普遍的癌症标志物,其在肿瘤组织和患者血清中的表达可预测癌症的严重程度(Tuszynski 等人,2011 年;Zheng 等人,2012 年;Zheng 2013 年;Chang 和 Tuszynski,2020 年)。在初步研究结果中,我们发现 GASP-1 抗体抑制了三阴性乳腺癌 MDA-MB-231 细胞系的生长,并且这些细胞中 GASP-1 的短暂减少降低了其增殖能力。为了进一步证实这些结果,我们在 MDA-MB-231 细胞的稳定克隆中过表达和低表达 GASP-1,并评估它们的生长和侵袭活性。在培养 4 天后,低表达 GASP-1 的细胞无法生长,最终死亡。相比之下,表达 GASP-1 的细胞呈指数级生长。同样,低表达 GASP-1 的细胞在软琼脂中形成的菌落数量比对照减少 30%,而高表达 GASP-1 的细胞形成的菌落数量比对照增加 2 倍。在肿瘤细胞侵袭实验中,高表达 GASP-1 的细胞比对照细胞的侵袭能力高出 10 倍以上,而低表达 GASP-1 的细胞比对照细胞的侵袭能力低 10 倍以上。在乳腺癌细胞的 IHC 染色研究中,我们发现过度表达的 GASP-1 出现在不同大小的颗粒中,这些颗粒与癌症的侵袭性直接相关。我们的研究结果强烈表明,GASP-1 促进了三阴性乳腺癌细胞系 MDA-MB-231 的增殖和侵袭,针对 GASP-1 进行治疗可能是治疗乳腺癌的一种方法。