Apoptotic cells contribute to melanoma progression and this effect is partially mediated by the platelet-activating factor receptor.

Apoptotic cells contribute to melanoma progression and this effect is partially mediated by the platelet-activating factor receptor.
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DOI:
10.1155/2012/610371
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发表时间:
2012
影响因子:
4.6
通讯作者:
Jasiulionis MG
Jasiulionis MG
中科院分区:
医学3区
文献类型:
--
作者:
Bachi AL;Dos Santos LC;Nonogaki S;Jancar S;Jasiulionis MG

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有证据表明血小板激活因子受体(PAFR)参与巨噬细胞清除凋亡细胞,并且这与抗炎表型相关。我们的小组之前已经证明,共注射大量凋亡细胞可以促进亚致瘤剂量的黑色素瘤细胞的肿瘤生长。在这里,我们研究了 PAFR 在凋亡细胞的肿瘤生长促进作用中的作用。将亚致瘤剂量的黑色素瘤细胞 (Tm1) 与凋亡 Tm1 细胞共同注射到 C57Bl/6 小鼠胁腹皮下,并监测体积 30 天。动物通过瘤周每日注射连续5天接受PAFR拮抗剂WEB2170或PCA4248(5mg/kg体重)或媒介物。结果表明,PAFR 拮抗剂显着抑制由亚致瘤剂量的黑色素瘤细胞与凋亡细胞共注射诱导的肿瘤生长。这伴随着早期中性粒细胞和巨噬细胞浸润的抑制。向该系统中添加(血小板激活因子)没有显着效果。 PAFR拮抗剂不影响角叉菜胶的促进作用。我们认为吞噬细胞对凋亡细胞的识别导致 PAFR 途径的激活,从而产生有利于黑色素瘤生长的微环境反应。
There is evidence that the platelet-activating factor receptor (PAFR) is involved in the clearance of apoptotic cells by macrophages, and that this is associated with anti-inflammatory phenotype. Our group has previously shown that coinjection of a large number of apoptotic cells can promote tumor growth from a subtumorigenic dose of melanoma cells. Here, we studied the involvement of the PAFR in the tumor growth promoting effect of apoptotic cells. A sub-tumorigenic dose of melanoma cells (Tm1) was coinjected with apoptotic Tm1 cells, subcutaneously in the flank of C57Bl/6 mice, and the volume was monitored for 30 days. Animals received the PAFR antagonists, WEB2170 or PCA4248 (5 mg/kg body weight) or vehicle, by peritumoral daily injection for 5 days. Results showed that PAFR antagonists significantly inhibited the tumor growth induced by the coinjection of a sub-tumorigenic dose of melanoma cells together with apoptotic cells. This was accompanied by inhibition of early neutrophil and macrophage infiltration. Addition of (platelet-activating factor) to this system has no significant effect. PAFR antagonists did not affect the promoting effect of carrageenan. We suggest that the recognition of apoptotic cells by phagocytes leads to activation of PAFR pathways, resulting in a microenvironment response favorable to melanoma growth.
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发表时间: 2006-03-01
期刊: NEOPLASIA
影响因子: 4.8
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发表时间: 2001-05-17
期刊: NATURE
影响因子: 64.8
作者:
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通讯作者: Kohn, EC