London C A, Kisseberth W C, Galli S J, Geissler E N, Helfand S C
Graduate Program in Immunology, Harvard Medical School, Boston, MA USA.
J Comp Pathol. 1996 Nov;115(4):399-414. doi: 10.1016/s0021-9975(96)80074-0.
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.
干细胞因子受体（SCFR，c-kit）通常在造血细胞和肥大细胞上表达，在细胞生长和分化中起调节作用。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瘤中获取的恶性犬肥大细胞上SCFR的表达，以确定这些未分化细胞是否维持这种促生长细胞因子受体的表达。从犬类患者的皮肤肿瘤或淋巴结转移灶中收集恶性肥大细胞（组织学2级），并通过对这些细胞的流式细胞术分析检测SCFR。所有肿瘤均与小鼠和犬重组干细胞因子（SCF）结合，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犬IgE的免疫球蛋白Fc受体，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瘤活检组织进行免疫组织化学分析，证实每个肿瘤的恶性细胞均表达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免疫标记的强度相关，表明不同肿瘤之间SCFR表达存在差异。从每个肿瘤获得的SCFR逆转录-聚合酶链反应产物的琼脂糖凝胶电泳具有根据小鼠和人类对应物预测的犬SCFR cDNA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一种能够触发细胞生长的膜受体，提示该受体在犬肥大细胞癌的病因学中起作用。犬类这种相对常见的恶性肿瘤似乎为研究SCF/SCFR途径在肥大细胞自发性恶性肿瘤发生中的潜在作用提供了机会。
