Breast cancer is one of the most common forms of cancer affecting women in the United States, second only to skin cancers. Although treatments have been developed to combat primary breast cancer, metastasis remains a leading cause of death. An early step of metastasis is cancer cell invasion through the basement membrane. However, this process is not yet well understood. AG73, a synthetic laminin-α1 chain peptide, plays an important role in cell adhesion and has previously been linked to migration, invasion, and metastasis. Thus, we aimed to identify the binding partner of AG73 on breast cancer cells that could mediate cancer progression. We performed adhesion assays using MCF10A, T47D, SUM1315, and MDA-231 breast cell lines and found that AG73 binds to syndecans (Sdcs) 1, 2, and 4. This interaction was inhibited when we silenced Sdcs 1 and/or 4 in MDA-231 cells, indicating the importance of these receptors in this relationship. Through actin staining, we found that silencing of Sdc 1, 2, and 4 expression in MDA-231 cells exhibits a decrease in the length and number of filopodia bound to AG73. Expression of mouse Sdcs 1, 2, and 4 in MDA-231 cells provides rescue in filopodia, and overexpression of Sdcs 1 and 2 leads to increased filopodium length and number. Our findings demonstrate an intrinsic interaction between AG73 in the tumor environment and the Sdcs on breast cancer cells in supporting tumor cell adhesion and invasion through filopodia, an important step in cancer metastasis.

中文翻译：

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层粘连蛋白-α1链衍生肽AG73与MDA-231乳腺癌细胞上的Syndecans结合，并改变成纤维细胞的形成。

乳腺癌是在美国影响女性的最常见癌症之一，仅次于皮肤癌。尽管已开发出抗击原发性乳腺癌的疗法，但转移仍然是主要的死亡原因。转移的早期步骤是癌细胞通过基底膜侵入。但是，此过程尚未很好地理解。AG73，一种合成层粘连蛋白-α1链肽在细胞黏附中起重要作用，以前与迁移，侵袭和转移有关。因此，我们旨在鉴定AG73在可介导癌症进展的乳腺癌细胞上的结合伴侣。我们使用MCF10A，T47D，SUM1315和MDA-231乳腺癌细胞系进行了粘附测定，结果发现AG73结合到Syndecans（Sdcs）1、2和4。当我们沉默MDA中的Sdcs 1和/或4时，这种相互作用被抑制了。 -231细胞，表明这些受体在这种关系中的重要性。通过肌动蛋白染色，我们发现MDA-231细胞中Sdc 1、2和4表达的沉默表现出与AG73结合的丝状伪足的长度和数量的减少。小鼠Sdc 1、2和4在MDA-231细胞中的表达可帮助丝状伪足，Sdc 1和Sdc 2的过表达导致fi的长度和数量增加。我们的发现表明，肿瘤环境中的AG73与乳腺癌细胞上的Sdc之间存在内在的相互作用，以支持肿瘤细胞通过丝状伪足的粘附和侵入，这是癌症转移的重要步骤。