FACS QUANTITATION OF LEUCINE AMINOPEPTIDASE AND ACID-PHOSPHATASE ON TUMOR-ASSOCIATED MACROPHAGES FROM METASTATIC AND NONMETASTATIC MOUSE MAMMARY-TUMORS

FACS QUANTITATION OF LEUCINE AMINOPEPTIDASE AND ACID-PHOSPHATASE ON TUMOR-ASSOCIATED MACROPHAGES FROM METASTATIC AND NONMETASTATIC MOUSE MAMMARY-TUMORS
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DOI:
10.1002/jlb.38.5.573
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发表时间:
1985-01-01
影响因子:
5.5
通讯作者:
HEPPNER, GH
HEPPNER, GH
中科院分区:
医学3区
文献类型:
--
作者:
MAHONEY, KH;MILLER, BE;HEPPNER, GH

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巨噬细胞通过粘附从许多小鼠乳腺癌细胞系产生的肿瘤中分离,并通过荧光激活细胞分选进行亮氨酸氨肽酶和酸性磷酸酶的定量检测。肿瘤包括3个细胞系66、67和168,它们最初来源于BALB/cfC 3 H小鼠中的单个自发产生的肿瘤,以及另外2个细胞系D2 A1和D2 F2,它们来源于可移植增生性肺泡结节细胞系D2产生的单个肿瘤。这5个细胞系在许多特征上彼此不同,包括从皮下植入物自发转移到肺部的能力以及静脉注射后在肺部形成实验性转移的能力。细胞系67在两种情况下都是非转移性的,而细胞系66、D2 A1和D2 F2在相同条件下是转移性的。在这些之间的是线168,其从皮下部位是非转移性的,但是当IV注射时能够以类似于66的效率定殖于肺。细胞系66、D2 A1和D2 F2的肿瘤相关巨噬细胞(TAM)中亮氨酸氨肽酶(Leu)含量最高,细胞系67的最低,细胞系168的TAM居中。相反,来自品系67的TAM具有最大量的酸性磷酸酶(APTase),而来自品系168的TAM具有最少量的酸性磷酸酶。除了粘附的TAM的酶水平在肿瘤之间的差异外,粘附的TAM的百分比在肿瘤之间也不同。在粘附部分中仅回收了来自管线67的12%的TAM,而来自管线66和168的TAM为35-38%。这些结果证实并扩展了我们先前的发现,即与来自非转移性肿瘤的TAM相比,来自转移性肿瘤的TAM具有增加的TNF水平。他们还证明了TAM中的APTase和APTase的非协调表达,并说明了TAM群体如何对一种酶是同质的,而对另一种酶是异质的。此外,转移性和非转移性肿瘤之间粘附的巨噬细胞百分比的差异是TAM的异质性和肿瘤在确定与其相关的宿主浸润类型中的作用的另一个指示。
Macrophages were isolated by adherence from tumors produced by a number of murine mammary carcinoma lines and were examined by fluorescence-activated cell sorting for quantitation of leucine aminopeptidase and acid phosphatase. The tumors included 3 lines, 66, 67, and 168, which were originally derived from a single, spontaneously arising tumor in a BALB/cfC3H mouse and 2 other lines, D2A1 and D2F2, which were derived from a single tumor arising from the transplantable hyperplastic alveolar nodule line, D2. These 5 lines differ from one another in a number of characteristics, including the ability to metastasize spontaneously to the lung from subcutaneous implants and to form experimental metastases in lungs following intravenous injection. Line 67 is nonmetastatic under both circumstances, whereas lines 66, D2A1, and D2F2 are metastatic under the same conditions. Intermediate to these is line 168, which is nonmetastatic from the subcutaneous site but capable of colonizing the lung with an efficiency similar to 66 when injected IV. Tumor-associated macrophages (TAM) from lines 66, D2A1, and D2F2 contained the greast amounts of leucine aminopeptidase (LAP) and those from line 67 the least, with TAM from 168 being intermediate. Conversely, the TAM from line 67 had the greatest amounts of acid phosphatase (APTase) and those from line 168 the least. In addition to differences among tumors in enzyme levels of the adherent TAM, the percentages of TAM that were adherent were also differnet among the tumors. Only 12% of TAM from line 67 were recovered in the adherent fraction as opposed to 35-38% of TAM from lines 66 and 168. These results confirm and extend our previous findings that TAM from metastatic tumors have increased levels of LAP compared to TAM from nonmetastatic tumors. They also demonstrate noncoordinate expression of LAP and APTase in TAM, and illustrate how a population of TAM can be homogeneous for 1 enzyme and heterogeneous for another. Furthermore, the difference in the percentage of macrophages that are adherent between metastatic and nonmetastic tumors is another indication both of the heterogeneous nature of TAM and of the role of a tumor in determining the type of host infiltrate with which it is associated.