Role of DDR1 in the gelatinases secretion induced by native type IV collagen in MDA-MB-231 breast cancer cells
Role of DDR1 in the gelatinases secretion induced by native type IV collagen in MDA-MB-231 breast cancer cells
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DOI：
10.1007/s10585-011-9385-9
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发表时间：
2011-06-01
影响因子：
4
通讯作者：
Perez Salazar, Eduardo
中科院分区：
文献类型：
--
作者：
Castro-Sanchez, Luis;Soto-Guzman, Adriana;Perez Salazar, Eduardo
盘状结构域受体（DDRs）是由天然三螺旋形式的胶原激活的受体酪氨酸激酶。在哺乳动物细胞中，DDR家族由两个成员组成，即DDR 1和DDR2，其介导多种细胞类型的迁移和增殖。DDR 1被天然IV型胶原激活，并在人乳腺癌中过表达。IV型胶原是基底膜（BM）的主要成分，降解和穿透BM的能力与侵袭和转移的可能性增加有关。基质金属蛋白酶（MMP）是锌依赖性内肽酶家族，其共同能够降解细胞外基质的所有组分，包括BM。在乳腺癌细胞中，变性IV型胶原诱导MMP-9分泌和侵袭。然而，DDR 1在调节明胶酶（MMP-2和-9）分泌和乳腺癌细胞侵袭中的作用仍有待研究。我们在这里证明，天然IV型胶原诱导MMP-2和-9分泌和入侵通过DDR 1和Src依赖性途径，连同MMP-2和-9细胞表面水平的增加。MMP-2和MMP-9的分泌需要PKC激酶活性、表皮生长因子受体（EGFR）活化、花生四烯酸（AA）产生和MDA-MB-231乳腺癌细胞中的AA代谢物。总之，我们的数据表明，第一次，DDR 1介导MMP-2和-9分泌和侵袭诱导的天然IV型胶原在MDA-MB-231乳腺癌细胞。
Discoidin domain receptors (DDRs) are receptor tyrosine kinases that get activated by collagens in its native triple-helical form. In mammalian cells, DDR family consists of two members, namely DDR1 and DDR2, which mediates migration and proliferation of several cell types. DDR1 is activated by native type IV collagen and overexpressed in human breast cancer. Type IV collagen is the main component of basement membrane (BM), and the ability to degrade and penetrate BM is related with an increased potential for invasion and metastasis. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that collectively are capable of degrading all components of the extracellular matrix, including the BM. In breast cancer cells, denatured type IV collagen induces MMP-9 secretion and invasion. However, the role of DDR1 in the regulation of gelatinases (MMP-2 and -9) secretion and invasion in breast cancer cells remains to be studied. We demonstrate here that native type IV collagen induces MMP-2 and -9 secretions and invasion through a DDR1 and Src-dependent pathway, together with an increase of MMP-2 and -9-cell surface levels. MMP-2 and -9 secretions require PKC kinase activity, epidermal growth factor receptor (EGFR) activation, arachidonic acid (AA) production and AA metabolites in MDA-MB-231 breast cancer cells. In summary, our data demonstrate, for the first time, that DDR1 mediates MMP-2 and -9 secretions and invasion induced by native type IV collagen in MDA-MB-231 breast cancer cells.