Bumaschny Viviana, Urtreger Alejandro, Diament Miriam, Krasnapolski Martín, Fiszman Gabriel, Klein Slobodanka, Joffé Elisa Bal de Kier
Research Area, Institute of Oncology Angel H, Roffo, University of Buenos Aires, Argentina.
Breast Cancer Res. 2004;6(2):R116-29. doi: 10.1186/bcr757. Epub 2004 Jan 15.
The normal duct and lobular system of the mammary gland is lined with luminal and myoepithelial cell types. Although evidence suggests that myoepithelial cells might suppress tumor growth, invasion and angiogenesis, their role remains a major enigma in breast cancer biology and few models are currently available for exploring their influence. Several years ago a spontaneous transplantable mammary adenocarcinoma (M38) arose in our BALB/c colony; it contains a malignant myoepithelial cell component and is able to metastasize to draining lymph nodes and lung.
To characterize this tumor further, primary M38 cultures were established. The low-passage LM38-LP subline contained two main cell components up to the 30th subculture, whereas the higher passage LM38-HP subline was mainly composed of small spindle-shaped cells. In addition, a large spindle cell clone (LM38-D2) was established by dilutional cloning of the low-passage MM38-LP cells. These cell lines were studied by immunocytochemistry, electron microscopy and ploidy, and syngeneic mice were inoculated subcutaneously and intravenously with the different cell lines, either singly or combined to establish their tumorigenic and metastatic capacity.
The two subpopulations of LM38-LP cultures were characterized as luminal and myoepithelium-like cells, whereas LM38-HP was mainly composed of small, spindle-shaped epithelial cells and LM38-D2 contained only large myoepithelial cells. All of them were tumorigenic when inoculated into syngeneic mice, but only LM38-LP cultures containing both conserved luminal and myoepithelial malignant cells developed aggressive papillary adenocarcinomas that spread to lung and regional lymph nodes.
The differentiated histopathology and metastatic ability of the spontaneous transplantable M38 murine mammary tumor is associated with the presence and/or interaction of both luminal and myoepithelial tumor cell types.
乳腺的正常导管和小叶系统由腔上皮细胞和肌上皮细胞类型构成。尽管有证据表明肌上皮细胞可能抑制肿瘤生长、侵袭和血管生成，但其在乳腺癌生物学中的作用仍是一个主要谜团，目前几乎没有模型可用于探究其影响。几年前，我们的BALB/c种群中出现了一种自发可移植性乳腺腺癌（M38）；它含有恶性肌上皮细胞成分，能够转移至引流淋巴结和肺。
为进一步表征该肿瘤，建立了原发性M38培养物。低传代的LM38-LP亚系在第30代传代之前包含两种主要细胞成分，而高传代的LM38-HP亚系主要由小的梭形细胞组成。此外，通过对低传代MM38-LP细胞进行稀释克隆建立了一个大的梭形细胞克隆（LM38-D2）。通过免疫细胞化学、电子显微镜和倍性分析对这些细胞系进行研究，并将不同的细胞系单独或联合皮下和静脉接种到同基因小鼠中，以确定它们的致瘤和转移能力。
LM38-LP培养物的两个亚群被表征为腔上皮样细胞和肌上皮样细胞，而LM38-HP主要由小的梭形上皮细胞组成，LM38-D2仅包含大的肌上皮细胞。将它们接种到同基因小鼠中时均具有致瘤性，但只有包含保留的腔上皮和肌上皮恶性细胞的LM38-LP培养物会发展为侵袭性乳头状腺癌，并扩散至肺和区域淋巴结。
自发可移植性M38小鼠乳腺肿瘤的分化组织病理学和转移能力与腔上皮和肌上皮肿瘤细胞类型的存在和/或相互作用有关。
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