Steinert Matthias, Wobus Manja, Boltze Carsten, Schütz Alexander, Wahlbuhl Mandy, Hamann Jörg, Aust Gabriela
Department of Surgery, University of Leipzig, Germany.
Am J Pathol. 2002 Nov;161(5):1657-67. doi: 10.1016/S0002-9440(10)64443-4.
The expression of CD97, a member of the EGF-TM7 family with adhesive properties, is proportional to the aggressiveness and lymph node involvement in thyroid tumors. CD97 has never been systematically investigated in other tumors. First, we examined colorectal carcinoma cell lines (n = 18) for CD97 expression and regulation. All cell lines were CD97-positive. The level of CD97 in each line correlated with migration and invasion in vitro. This result was confirmed in CD97-inducible Tet-off HT1080 cells. Transforming growth factor-beta, which inhibits proliferation in transforming growth factor-beta-sensitive LS513 and LS1034 cells, down-regulated CD97 in these cell lines. Examining CD97 during sodium butyrate-induced cell differentiation of Caco-2 cells, we could demonstrate a CD97-decreasing effect. Second, we screened 81 colorectal adenocarcinomas by immunohistology for expression of CD97. Normal colorectal epithelium is CD97-negative. Seventy-five of 81 of the carcinomas expressed CD97. The strongest staining for CD97 occurred in scattered tumor cells at the invasion front compared to cells located within solid tumor formations of the same tumor. Carcinomas with more strongly CD97-stained scattered tumor cells showed a poorer clinical stage as well as increased lymph vessel invasion compared to cases with uniform CD97 staining. In summary, CD97 expression correlates with dedifferentiation, migration, and invasion in colorectal tumor cell lines. Moreover, more strongly CD97-stained tumor cells at the invasion front of colorectal carcinomas indicate the involvement of the molecule in tumor migration and invasion.
CD97是具有黏附特性的表皮生长因子跨膜7家族成员之一，其表达与甲状腺肿瘤的侵袭性和淋巴结受累情况成正比。CD97从未在其他肿瘤中进行过系统研究。首先，我们检测了18种结肠癌细胞系的CD97表达及调控情况。所有细胞系均为CD97阳性。各细胞系中CD97的水平与体外迁移和侵袭相关。这一结果在可诱导表达CD97的Tet-off HT1080细胞中得到证实。转化生长因子-β可抑制对其敏感的LS513和LS1034细胞的增殖，并下调这些细胞系中的CD97。在丁酸钠诱导Caco-2细胞分化过程中检测CD97，我们发现其有降低CD97的作用。其次，我们通过免疫组织化学方法筛查了81例结肠腺癌的CD97表达情况。正常结肠上皮CD97阴性。81例腺癌中有75例表达CD97。与同一肿瘤实体瘤内的细胞相比，CD97染色最强的是侵袭前沿散在的肿瘤细胞。与CD97染色均匀的病例相比，散在肿瘤细胞CD97染色更强的腺癌临床分期更差，淋巴管侵犯也增加。总之，CD97表达与结肠肿瘤细胞系的去分化、迁移和侵袭相关。此外，结肠腺癌侵袭前沿CD97染色更强的肿瘤细胞表明该分子参与了肿瘤的迁移和侵袭。
