O'Hayre Morgan, Salanga Catherina L, Handel Tracy M, Allen Samantha J
Skaggs School of Pharmacy and Pharmaceutical Science, University of California San Diego, La Jolla, CA 92093-0684, USA.
Biochem J. 2008 Feb 1;409(3):635-49. doi: 10.1042/BJ20071493.
Inappropriate chemokine/receptor expression or regulation is linked to many diseases, especially those characterized by an excessive cellular infiltrate, such as rheumatoid arthritis and other inflammatory disorders. There is now overwhelming evidence that chemokines are also involved in the progression of cancer, where they function in several capacities. First, specific chemokine-receptor pairs are involved in tumour metastasis. This is not surprising, in view of their role as chemoattractants in cell migration. Secondly, chemokines help to shape the tumour microenvironment, often in favour of tumour growth and metastasis, by recruitment of leucocytes and activation of pro-inflammatory mediators. Emerging evidence suggests that chemokine receptor signalling also contributes to survival and proliferation, which may be particularly important for metastasized cells to adapt to foreign environments. However, there is considerable diversity and complexity in the chemokine network, both at the chemokine/receptor level and in the downstream signalling pathways they couple into, which may be key to a better understanding of how and why particular chemokines contribute to cancer growth and metastasis. Further investigation into these areas may identify targets that, if inhibited, could render cancer cells more susceptible to chemotherapy.
趋化因子/受体的表达或调控异常与许多疾病相关，尤其是那些以细胞浸润过多为特征的疾病，如类风湿性关节炎和其他炎症性疾病。现在有大量证据表明趋化因子也参与癌症进展，它们在其中发挥多种作用。首先，特定的趋化因子-受体对参与肿瘤转移。鉴于它们在细胞迁移中作为化学引诱剂的作用，这并不奇怪。其次，趋化因子通过募集白细胞和激活促炎介质，有助于塑造肿瘤微环境，通常有利于肿瘤生长和转移。新出现的证据表明，趋化因子受体信号传导也有助于细胞存活和增殖，这对于转移细胞适应外部环境可能尤为重要。然而，趋化因子网络在趋化因子/受体水平以及它们所连接的下游信号通路方面都存在相当大的多样性和复杂性，这可能是更好地理解特定趋化因子如何以及为何促进癌症生长和转移的关键。对这些领域的进一步研究可能会确定一些靶点，如果对其进行抑制，可能会使癌细胞对化疗更敏感。
