Grudowska Alicja, Czaplińska Dominika, Polom Wojciech, Matuszewski Marcin, Sądej Rafał, Składanowski Andrzej C
Department of Molecular Enzymology, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Gdańsk, Poland.
Department of Cell Biology, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Gdańsk, Poland.
Acta Biochim Pol. 2017;64(1):135-141. doi: 10.18388/abp.2016_1356. Epub 2017 Mar 14.
Invasion and migration of cancer cells are crucial for the formation of secondary lesions. These require activation of signalling cascades modulated by the number of regulatory molecules. One such molecule is CD151, a member of evolutionary conserved tetraspanin family. CD151 is involved in cell adhesion, motility and cancer progression due to formation of complexes with laminin-binding integrins and regulation of growth factor receptors function (e.g. HGFR, TGFβR, EGFR). Recent studies point to correlation between CD151 expression and high tumour grade in prostate cancer (PCa). Herein, we investigated a possible role of CD151 in communication between PC3 cancer cells and either cancer-associated fibroblasts (CAFs) or osteoblasts, an interplay which is significant for metastasis. The analysis showed that although CAFs strongly enhanced both migration and invasion of PC3 prostate cancer cells, the effect was not dependent on CD151. On the other hand, CD151 was found to promote 3D migration as well as invasive growth in response to osteoblasts-secreted growth factors. Obtained data revealed that knockdown of CD151 abolished activation of pro-migratory/pro-survival kinases (i.e FAK, Src, HSP27) triggered by osteoblasts, along with expression of matrix metalloproteinase-13. This suggests that CD151 participates in communication between PC3 cells and bone microenvironment and the process can be considered as a significant step of PCa progression and metastasis.
癌细胞的侵袭和迁移对于继发性病变的形成至关重要。这些过程需要由多种调节分子调控的信号级联反应的激活。其中一种分子是CD151，它是进化保守的四跨膜蛋白家族的成员。由于与层粘连蛋白结合整合素形成复合物并调节生长因子受体功能（如HGFR、TGFβR、EGFR），CD151参与细胞粘附、运动和癌症进展。最近的研究指出CD151表达与前列腺癌（PCa）的高肿瘤分级之间存在相关性。在此，我们研究了CD151在PC3癌细胞与癌症相关成纤维细胞（CAFs）或成骨细胞之间通讯中可能发挥的作用，这种相互作用对转移具有重要意义。分析表明，尽管CAFs强烈增强了PC3前列腺癌细胞的迁移和侵袭，但这种作用并不依赖于CD151。另一方面，发现CD151可促进对成骨细胞分泌的生长因子作出反应的三维迁移以及侵袭性生长。获得的数据显示，敲低CD151可消除由成骨细胞触发的促迁移/促存活激酶（即FAK、Src、HSP27）的激活以及基质金属蛋白酶-13的表达。这表明CD151参与PC3细胞与骨微环境之间的通讯，并且该过程可被视为PCa进展和转移的重要步骤。
