Expression of stem cell factor receptor (c-kit) by the malignant mast cells from spontaneous canine mast cell tumours
Expression of stem cell factor receptor (c-kit) by the malignant mast cells from spontaneous canine mast cell tumours
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DOI：
10.1016/s0021-9975(96)80074-0
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发表时间：
1996-11-01
影响因子：
0.8
通讯作者：
Helfand, SC
中科院分区：
文献类型：
--
作者：
London, CA;Kisseberth, WC;Helfand, SC
干细胞因子受体（SCFR，c-kit）通常表达于造血细胞和肥大细胞，在细胞生长和分化中发挥调节作用。 SCFR 表达失调可能导致肿瘤转化。我们研究了直接从自发性犬肥大细胞肿瘤中获得的恶性犬肥大细胞上 SCFR 的表达，试图确定这些未分化的细胞是否维持了这种促进生长的细胞因子受体的表达。从犬患者身上收集来自皮肤肿瘤或淋巴结转移的恶性肥大细胞（组织学等级 2），并通过流式细胞术分析这些细胞来检测 SCFR。所有肿瘤均结合小鼠和犬重组干细胞因子（SCF），表明这些细胞不仅表达 SCFR，而且受体具有配体结合的功能特性。通过流式细胞术在这些细胞上鉴定出了犬 IgE 的免疫球蛋白 Fc 受体，这进一步表明所分析的细胞是肥大细胞并保留了一些分化特征。对福尔马林固定、石蜡包埋的肥大细胞肿瘤活组织检查进行的免疫组织化学分析证实了每个肿瘤的恶性细胞表达 SCFR。通过流式细胞术评估，SCF 与肿瘤细胞悬液的相对结合与同一肿瘤切片中 SCFR 的免疫标记强度相关，表明肿瘤之间 SCFR 表达的变异性。来自每个肿瘤的 SCFR 逆转录聚合酶链式反应产物的琼脂糖凝胶电泳具有基于小鼠和人类对应物预测的犬 SCFR cDNA 的分子量。这进一步证实了恶性犬肥大细胞表达SCFR。综上所述，这些结果表明，恶性犬肥大细胞表达能够触发细胞生长的膜受体，表明该受体在犬肥大细胞癌的病因学中发挥作用。这种相对常见的狗恶性肿瘤似乎为研究 SCF/SCFR 通路在肥大细胞自发恶性肿瘤发展中的潜在作用提供了机会。 (C) 1996 W.B.桑德斯有限公司
Stem cell factor receptor (SCFR, c-kit), normally expressed on haematopoietic and mast cells, plays a regulatory role in cellular growth and differentiation. Dysregulated expression of SCFR may contribute to neoplastic transformation. We investigated expression of SCFR on malignant canine mast cells obtained directly from spontaneous canine mast cell neoplasms, in an attempt to determine whether these undifferentiated cells maintained expression of this growth-promoting cytokine receptor. Malignant mast cells (histological grade 2) from skin tumours or lymph node metastases were collected from canine patients, and SCFRs were detected by flow cytometric analysis of these cells. All of the tumours bound mouse and canine recombinant stem cell factor (SCF), indicating that the cells not only expressed SCFRs, but that the receptors possessed the functional property of ligand binding. Immunoglobulin Fc receptors for canine IgE were identified on these cells by flow cytometry, a further indication that the cells analysed were mast cells and retained some differentiated features. Immunohistochemical analysis of formalin-fixed, paraffin wax-embedded mast cell tumour biopsies confirmed expression of SCFRs by malignant cells from each tumour. The relative binding of SCF to suspensions of tumour cells, as assessed by flow cytometry, correlated with the intensity of immunolabelling for SCFR in sections of the same tumours, suggesting variability in SCFR expression between tumours. Agarose gel electrophoresis of the products of SCFR reverse transcription-polymerase chain reaction derived from each tumour had the molecular weight predicted for canine SCFR cDNA on the basis of the mouse and human counterparts. This further confirmed SCFR expression by malignant canine mast cells. Taken together, these results show that a membrane receptor capable of triggering cell growth is expressed by malignant canine mast cells, suggesting a role for this receptor in the aetiology of canine mast cell cancer. This relatively common malignancy of the dog would seem to present an opportunity for the investigation of the potential role of the SCF/ SCFR pathway in the development of spontaneous malignancies of mast cells. (C) 1996 W.B. Saunders Company Limited