CCR7 regulates B16 murine melanoma cell tumorigenesis in skin
CCR7 regulates B16 murine melanoma cell tumorigenesis in skin
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DOI：
10.1189/jlb.1107776
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发表时间：
2008-10-01
影响因子：
5.5
通讯作者：
Hwang, Sam T.
中科院分区：
文献类型：
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作者：
Fang, Lei;Lee, Vivian C.;Hwang, Sam T.
肿瘤细胞相关趋化因子受体在肿瘤生物学中起着独特的作用，包括增强淋巴结（LN）转移。为了确定CCR 7是否影响皮肤中的肿瘤形成，我们将用CCR 7和荧光素酶（CCR 7-luc-B16）或用逆转录病毒载体和荧光素酶（pLNCX 2-luc-B16）转导的B16细胞接种到野生型（WT）小鼠的耳皮肤和足垫中。与pLNCX 2-luc-B16细胞相反，到耳接种后第21天，97%的CCR 7-luc-B16细胞接种小鼠形成皮肤肿瘤以及颈部LN转移。然而，表达CCR 7的B16细胞和对照B16细胞在SCID-米色小鼠中形成了相似大小的肿瘤，并且具有高效率。两种细胞系的细胞在WT小鼠的皮肤中以相似的数量积累，直至第7天。然而，到第11天，对照细胞减少了10倍，而CCR 7-luc-B16细胞形成了小的肿瘤结节。在注射两种细胞系后11天内，在引流的颈部淋巴结中很少检测到肿瘤细胞，但仅在建立CCR 7-lucB 16耳肿瘤后观察到稳定的淋巴结转移（与第21天相似）。ELISPOT测定显示，到第7天，注射CCR 7-luc-B16的耳朵的引流淋巴结中产生IFN-γ的细胞减少。足垫注射后，CCR 7表达B16细胞的肿瘤形成仅在小的初始肿瘤细胞接种物下增强。在较大的接种物下，肿瘤形成是相等的，但与相同大小的pLNCX 2-B16肿瘤相比，CCR 7-B16肿瘤中肿瘤浸润性白细胞的数量减少了约6倍。在CCR 7-B16细胞肿瘤中，IFN-γ和CXCL 10分别减少了35倍和6倍（与对照肿瘤相比）。因此，CCR 7表达除了促进LN转移外还增强肿瘤发生。
Tumor cell-associated chemokine receptors play distinct roles in cancer biology, including enhancement of lymph node (LN) metastasis. To determine if CCR7 influences tumor formation in skin, we inoculated B16 cells transduced with CCR7 and luciferase (CCR7-luc-B16) or with retroviral vector and luciferase (pLNCX2-luc-B16) into ear skin and footpads of wild-type (WT) mice. In contrast to pLNCX2-luc-B16 cells, 97% of CCR7-luc-B16 cell-inoculated mice formed skin tumors as well as cervical LN metastases by Day 21 following ear inoculation. CCR7-expressing and control B16 cells, however, formed tumors of similar size and with high-efficiency in SCID-beige mice. Cells from both lines accumulated in the skin of WT mice in similar numbers until Day 7. By Day 11, however, control cells decreased tenfold, whereas CCR7-luc-B16 cells formed small tumor nodules. Tumor cells were infrequently detected in draining cervical LNs up to 11 days after injection of both cell lines, but stable nodal metastases were only observed after CCR7-lucB16 ear tumors had been established (similar to Day 21). ELISPOT assays revealed that IFN-gamma-producing cells in draining LNs from CCR7-luc-B16-injected ears were reduced through Day 7. After footpad injection, tumor formation by CCR7-expressing B16 cells was enhanced only with small, initial tumor cell inocula. With larger inocula, tumor formation was equivalent, but the numbers of tumor-infiltrating leukocytes were reduced by approximately sixfold in CCR7-B16 tumors compared with pLNCX2-B16 tumors of equal size. IFN-gamma and CXCL10 were reduced 35- and sixfold, respectively, in CCR7-B16 cell tumors (vs. control tumors). Thus, CCR7 expression enhances tumorigenesis in addition to facilitating LN metastasis.