The mouse mammary carcinoma 4T1:: characterization of the cellular landscape of primary tumours and metastatic tumour foci
The mouse mammary carcinoma 4T1:: characterization of the cellular landscape of primary tumours and metastatic tumour foci
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DOI：
10.1111/j.1365-2613.2007.00539.x
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发表时间：
2007-10-01
影响因子：
3
通讯作者：
Hunter, Kenneth W., Jr.
中科院分区：
文献类型：
--
作者：
DuPre, Sally A.;Redelman, Doug;Hunter, Kenneth W., Jr.
小鼠乳腺癌4 T1引起类白血病反应，伴有严重的粒细胞增多，同时产生肿瘤源性生长因子。在这里，我们研究了原发性肿瘤和转移性肿瘤病灶的细胞景观，并将造血细胞浸润与肿瘤源性趋化因子的产生相关联。在移植后不同时间对酶消化的原发性肿瘤进行流式细胞术分析，发现主要由CD 11b（+）髓系细胞组成的CD 45（+）造血细胞浸润逐渐增加。这些细胞中的大多数具有F4/80（+）/CD 11 c（+）表型，其中许多也染色Gr-1（+）。还鉴别出较少数量的Gr-1（+）CD 11b（+）粒细胞和淋巴样细胞。在转移性肿瘤病灶的肝和肺的酶促细胞因子中观察到Gr-1（+）粒细胞的进行性增加。培养的4 T1肿瘤细胞表达髓样细胞趋化因子RANTES、MCP-1和KC的mRNA转录物，并且来自部分去除CD 45（+）细胞的原代4 T1肿瘤的酶消化细胞表达这些趋化因子以及MIP-1 α和MIP-1 β的转录物。这些数据表明，4 T1荷瘤小鼠具有原发性肿瘤的混合髓样细胞浸润和转移性器官的粒细胞浸润。这种病理表现与肿瘤源性趋化因子的表达相关。
The murine mammary carcinoma 4T1 causes a leukemoid reaction with profound granulocytosis coincident with the production of tumour-derived growth factors. Here, we study the evolving cellular landscape of primary tumours and metastatic tumour foci and correlate haematopoietic cell infiltration with the production of tumour-derived chemokines. Flow cytometric analysis of enzyme digested primary tumours at different times after transplantation revealed a progressively increasing CD45(+) haematopoietic cell infiltrate consisting predominantly of CD11b(+) myeloid cells. Most of these cells had an F4/80(+)/CD11c(+) phenotype, many of which also stained Gr-1(+). Smaller numbers of Gr-1(+)CD11b(+) granulocytes and lymphoid cells were also identified. Progressive increases in Gr-1(+) granulocytes were observed in enzymatic digests of livers and lungs with metastatic tumour foci. Cultured 4T1 tumour cells expressed mRNA transcripts for the myeloid cell chemokines RANTES, MCP-1 and KC, and enzymatically digested cells from primary 4T1 tumours partially depleted of CD45(+) cells expressed transcripts for these chemokines and also MIP-1 alpha and MIP-1 beta. These data demonstrate that 4T1 tumour-bearing mice have mixed myeloid cell infiltrates of primary tumours and granulocytic infiltrates of metastatic organs. This pathologic presentation correlated with the expression of tumour-derived chemokines.