Anaplastic neoplasms arising from basal cellcarcinoma xenotransplants into SCID-beige mice
Anaplastic neoplasms arising from basal cellcarcinoma xenotransplants into SCID-beige mice
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DOI：
10.1034/j.1600-0560.2002.290502.x
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发表时间：
2002-05-01
影响因子：
1.7
通讯作者：
Prouty, SM
中科院分区：
文献类型：
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作者：
Carlson, JA;Combates, NJ;Prouty, SM
背景：为了更好地了解基底细胞癌（BCC）的生物学特性，需要一种研究BCC的动物模型。几次尝试生长BCC的免疫功能不全的动物只有适度successful.Methods：测试BCC的能力，生长在小鼠完全和严重的免疫功能不全，14个单独的BCC被移植到皮下组织的18个SCID-米色小鼠（T，B和自然杀伤细胞缺陷）。结果：3例BCC移植后均形成快速生长的间变性肿瘤，占18%（3/18）。没有肿瘤生长的SCID米色小鼠在移植部位主要有疤痕或表皮样囊肿。BCC引起间变性肿瘤的三名患者明显比没有肿瘤生长的患者年龄大（87 vs. 64，p = 0.001），但他们在BCC类型或一般健康状况方面没有差异。这三种间变性肿瘤在组织学和免疫表型上相似，均由表达波形蛋白和平滑肌肌动蛋白的异型细胞组成。在第一代小鼠中，这些肿瘤是局部侵袭性的肿瘤形成结节，与供体炎性细胞（T和B淋巴细胞和浆细胞）的扩增、罕见的BCC上皮残留物和表皮样囊肿相关。到第七代，肿瘤是同质的，并在整个小鼠中广泛转移。将移植位置改变到真皮到伤口环境或用BCC衍生的成纤维细胞补充肿瘤并没有改变SCID米色小鼠的表型或生长速率。间变性肿瘤也容易在SCID小鼠（T和B细胞缺陷）中生长。然而，间变性肿瘤移植到正常小鼠（CB-17）或不太严重的免疫缺陷小鼠（NCr和Balb/c：T和自然杀伤细胞缺陷）不允许生长。此外，肿瘤生长不能维持在vitro. Conclusion：经验上，这些数据表明，BCC有可能成为一个积极的转移性肿瘤，给予正确的免疫和基质环境。此外，功能性B淋巴细胞系统似乎可以防止这种生长。由于人淋巴细胞也移植到SCID-米色小鼠中，原始宿主免疫应答可能是大多数异种移植物中缺乏肿瘤生长的原因。此外，这些基底细胞癌衍生的肿瘤的间变性和转移表型可能是转移性基底细胞癌和基底细胞癌与癌肉瘤相关的实验等价物。
Background: An animal model for the study of basal cell carcinoma (BCC) is required to better understand its biology. Several attempts to grow BCC in immuno-incompetent animals have been only modestly successful.Methods: To test the ability of BCC to grow in a mouse with complete and severe immuno-incompetence, 14 individual BCC were transplanted into the subcutaneous tissue of 18 SCID-beige mice (T, B and natural killer cell deficient). Light microscopy and immunophenotypic analyses were performed on primary BCC and first and seventh passage tumors.Results: Transplantation of three BCC yielded rapidly growing anaplastic tumors for a tumor take of 18% (3/18). SCID-beige mice without tumor growth had mostly scars or epidermoid cysts at the transplant sites. The three patients whose BCC gave rise to the anaplastic tumors were significantly older than those without tumor growth (87 vs. 64, p = 0.001), but they did not differ with respect to BCC type or general health. These three anaplastic tumors were histologically and immunophenotypically similar, being composed of dyscohesive, pleomorphic cells that expressed vimentin and smooth muscle actin. In the first passage mice these tumors were locally invasive, tumor-forming nodules associated with an expansion of donor inflammatory cells (T and B lymphocytes and plasma cells), rare remnants of BCC epithelium and epidermoid cysts. By the seventh passage, the tumors were homogenous and metastasized widely throughout the mice. Changing transplantation location to the dermis to wound environment or supplementing the tumor with BCC-derived fibroblasts did not alter the phenotype or growth rate in SCID-beige mice. Anaplastic tumors also grew easily in SCID mice (T and B cell deficient). However, transplantation of the anaplastic tumors into normal mice (CB-17) or less severely immunodeficient mice (NCr and Balb/c: T and natural killer cell deficient) did not allow for growth. Furthermore, tumor growth could not be maintained in vitro .Conclusion: Empirically, these data suggest that BCC has the potential to become an aggressive metastatic neoplasm, given the right immune and stromal environment. Moreover, a functional B lymphocyte system appears to prevent this growth. As human lymphocytes also engraft in SCID-beige mice, the original host immune response could be responsible for the lack of tumor growth in the majority of xenografts. Furthermore, the anaplastic and metastatic phenotype of these BCC derived neoplasms may be the experimental equivalent of metastatic BCC and BCC associated with carcinosarcoma.