H-cadherin expression inhibits in vitro invasiveness and tumor formation in vivo
H-cadherin expression inhibits in vitro invasiveness and tumor formation in vivo
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DOI：
10.1093/carcin/19.6.1157
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发表时间：
1998-06-01
期刊：
影响因子：
4.7
通讯作者：
Kocher, O
中科院分区：
文献类型：
--
作者：
Lee, SW;Reimer, CL;Kocher, O
H-cadherin是一种新发现的钙粘蛋白分子，在多种人乳腺癌细胞中表达减少，提示其可能在维持正常细胞表型中起作用。为了研究H-cadherin的再表达对人乳腺癌细胞恶性表型的影响，我们将对照和H-cadherin表达载体转染人乳腺癌细胞（MDAMB 435），其不组成性表达H-钙粘蛋白。我们发现这些细胞的侵袭性可以通过转染H-cadherin来阻止。我们还比较了对照和H-cadherin转染的细胞注射到裸鼠乳腺脂肪垫后诱导皮下肿瘤的能力。我们的结果表明，H-钙粘蛋白转染对肿瘤生长产生了显著的抑制作用，并改变了肿瘤细胞的形态：来自注射对照细胞的小鼠的肿瘤明显更大，并且含有比由表达H-钙粘蛋白的癌细胞产生的肿瘤具有更高程度多形性的更大细胞。总之，这些结果表明H-钙粘蛋白表达拮抗裸鼠中的肿瘤生长，推测是通过增强组织环境中的细胞-细胞结合。这些发现有力地表明，H-钙粘蛋白可以提供一个可能的目标，对乳腺癌的纠正基因治疗。
H-cadherin is a newly characterized cadherin molecule whose expression is decreased in a variety of human carcinoma cells, suggesting that it may play a role in maintaining normal cellular phenotype, To investigate how re-expression of H-cadherin could influence the malignant phenotype of human breast carcinoma cells in vivo, we transfected both control and H-cadherin expression vectors into human breast cancer cells (MDAMB435), which do not express H-cadherin constitutively. We found that invasiveness of these cells could be prevented by transfection with H-cadherin, We also compared the ability of control- and H-cadherin-transfected cells to induce subcutaneous tumors after injection into mammary fat pads of nude mice. Our results show that H-cadherin transfection produced a marked inhibition of tumor growth and modified the morphology of tumor cells: tumors from mice injected with control cells were significantly larger and contained larger cells having a higher degree of pleomorphism than those of tumors generated from carcinoma cells expressing H-cadherin, Altogether, these results indicate that H-cadherin expression antagonizes tumor growth in nude mice, presumably by enhancing cell-cell association in a tissue environment. These findings strongly suggest that H-cadherin could provide a possible target for corrective gene therapy against breast cancer.