Metastasis and Angiogenesis Research Group, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK.
Anticancer Res. 2010 Apr;30(4):1163-8.
ALCAM, activated leukocyte cell adhesion molecule, is connected to the progression of certain solid tumours and has been shown to be a prominent feature for tumours that subsequently developed bone metastasis. The present study investigated the biological influence of ALCAM on breast cancer cells in connection with bone biological environment.
Suitable breast cancer cells were transfected with either the ALCAM expression construct or anti-ALCAM transgene, to create sublines that had differential expression of ALCAM. The growth, migration and invasion of the cells were evaluated in the presence or absence of matrix proteins prepared from human bones.
ZR-751(DeltaALCAM) (ALCAM knockdown) and MDA-MB-231(ALCAMexp) (overexpressing ALCAM) were constructed. MDA MB-231(ALCAMexp) cells showed a slower rate of growth compared with control cells. However, in the presence of bone matrix proteins, MDA MB-231(ALCAMexp) showed a significantly reduced rate of growth, p<0.01 vs. control cells. In contrast, ZR-751(DeltaALCAM) cells grew faster compared with control cells. MDA MB-231(ALCAMexp) displayed a significantly reduced (p=0.012) and ZR-751(DeltaALCAM) cells significantly increased invasiveness (p=0.02) vs. their respective controls cells. In an ECIS-based cell migration assay, MDA-MB-231(ALCAMexp) cells showed marked reduction in migration. Inclusion of bone matrix proteins therefore further reduced the migration speed of MDA MB-231(ALCAMexp) cells.
Loss of ALCAM in breast cancer cells facilitates the invasive behaviour of breast cancer and high levels of ALCAM in the cells have a suppressive role in the aggressive nature of breast cancer cells.
激活白细胞细胞黏附分子(ALCAM)与某些实体瘤的进展有关,并且已被证明是随后发生骨转移的肿瘤的突出特征。本研究探讨了 ALCAM 对乳腺癌细胞在骨生物环境中的生物学影响。
用 ALCAM 表达构建体或抗 ALCAM 转基因转染合适的乳腺癌细胞,以创建具有不同 ALCAM 表达的亚系。在存在或不存在从人骨制备的基质蛋白的情况下,评估细胞的生长、迁移和侵袭。
构建了 ZR-751(DeltaALCAM)(ALCAM 敲低)和 MDA-MB-231(ALCAMexp)(过表达 ALCAM)。与对照细胞相比,MDA-MB-231(ALCAMexp)细胞的生长速度较慢。然而,在存在骨基质蛋白的情况下,MDA-MB-231(ALCAMexp)细胞的生长速度明显降低,p<0.01 与对照细胞相比。相比之下,ZR-751(DeltaALCAM)细胞的生长速度比对照细胞快。MDA-MB-231(ALCAMexp)的侵袭性显著降低(p=0.012),而 ZR-751(DeltaALCAM)细胞的侵袭性显著增加(p=0.02)与各自的对照细胞相比。在基于 ECIS 的细胞迁移测定中,MDA-MB-231(ALCAMexp)细胞的迁移明显减少。包含骨基质蛋白进一步降低了 MDA-MB-231(ALCAMexp)细胞的迁移速度。
乳腺癌细胞中 ALCAM 的缺失促进了乳腺癌的侵袭行为,而细胞中高水平的 ALCAM 对乳腺癌细胞的侵袭性具有抑制作用。