Barkhordar R A, Berston E D, Ramos D M
Department of Restorative Dentistry, University of California, San Francisco, USA.
Eur J Cancer B Oral Oncol. 1995 Jan;31B(1):49-52. doi: 10.1016/0964-1955(94)00028-3.
Tumour cells spread from primary tumours to form distant metastatic deposits by both lymphatic and blood routes. Melanomas occurring in the head and neck have an extremely poor prognosis largely in part due to late detection resulting in extensive dissemination by lymphatic metastasis. The purpose of this study was to develop an animal model for the study of head and neck melanoma metastasis. B16-F1 parental cells were injected into the subcutis of the ear mid-lobule of C57BL/6 mice. At selected time periods after inoculation, animals were killed by cervical dislocation and autopsied. In some animals tumours had spread to the cervical lymph nodes. Examination of organ systems revealed no evidence of distant metastases. Histological examination of the cervical lymph nodes revealed tumour invasion, beginning at a subcapsular sinus and progressing into the paracortical sinuses. Cells from these nodes were adapted to cell culture, expanded by passage and reinjected into new mice. Subsequent generations of lymph node-selected B16 cell lines were more metastatic than their parental cell line, as evidenced by a more rapid appearance of cervical lymph node and extensive node invasion. Morphologically, the lymph node-selected B16 cell lines were more dendritic than the original B16-F1 parent line and had a larger number of pseudopodial projections. Perhaps increased expression of pseudopods by the metastatic variants may allow for greater migratory potential and hence increased metastatic ability. These results indicate that highly mobile variant B16 sublines can be selected with an increased capacity for cervical lymphatic metastasis.
肿瘤细胞通过淋巴和血液途径从原发性肿瘤扩散，形成远处转移灶。头颈部发生的黑色素瘤预后极差，很大程度上是由于发现较晚，导致通过淋巴转移广泛扩散。本研究的目的是建立一种用于研究头颈部黑色素瘤转移的动物模型。将B16 - F1亲代细胞注射到C57BL / 6小鼠耳中叶的皮下。接种后在选定的时间段，通过颈椎脱臼处死动物并进行尸检。在一些动物中，肿瘤已扩散至颈部淋巴结。对各器官系统的检查未发现远处转移的迹象。对颈部淋巴结的组织学检查显示有肿瘤浸润，始于被膜下窦并向副皮质窦发展。从这些淋巴结获取的细胞适应细胞培养，通过传代扩增后再注射到新的小鼠体内。后续几代经淋巴结筛选的B16细胞系比其亲代细胞系更具转移性，表现为颈部淋巴结出现更快且有广泛的淋巴结浸润。形态学上，经淋巴结筛选的B16细胞系比原始的B16 - F1亲代细胞系更具树突状，且有更多的伪足突起。转移性变体增加的伪足表达可能使其具有更大的迁移潜力，从而增强转移能力。这些结果表明，可以选择出具有增强的颈部淋巴转移能力的高迁移性B16亚系。
