Pence Kristi A, Mishra Dhruva K, Thrall Michael, Dave Bhuvanesh, Kim Min P
Department of Surgery, Houston Methodist Hospital Research Institute, Houston, Texas.
Department of Pathology and Genomic Medicine, Houston Methodist Hospital Research Institute, Houston, Texas.
J Surg Res. 2017 Apr;210:181-187. doi: 10.1016/j.jss.2016.11.019. Epub 2016 Nov 17.
Breast cancer mortality is most common in cancer in women, and there are no ex vivo models that can capture the primary growth of tumor with fidelity to the in vivo tumor growth. In this study, we grew human breast cancer cell lines in an acellular lung matrix of the ex vivo four-dimensional lung model to determine if they form primary tumor and the extent to which they mimic the histology and characteristics of the human tumors.
Rat lungs were harvested, decellularized, and placed in a bioreactor. To study the primary tumor growth, we seeded the lung via the trachea with human breast cancer cells SUM159, MCF7, or MDMB231 and perfused the pulmonary artery with oxygenated media. Lobectomies were performed and processed for hematoxylin and eosin, Ki-67, caspase-3, estrogen receptor, and progesterone receptor antibodies.
All three cell lines grew in the ex vivo four-dimensional model and formed perfusable tumor nodules with similar histology and morphology as the primary tumors. SUM159 and MDAMB231 showed higher proliferation and apoptotic indices than MCF7. In addition, MCF7 retained its estrogen receptor and progesterone receptor positivity, whereas SUM159 and MDAMB 231 did not have any staining.
Overall, our study showed that human breast cancer cells can be grown on the ex vivo four-dimensional lung model, which then form primary tumor nodules that mimic the morphology and histology of the original tumor.
乳腺癌死亡率在女性癌症中最为常见,目前尚无能够忠实地模拟体内肿瘤生长的体外模型来捕捉肿瘤的原发生长情况。在本研究中,我们将人乳腺癌细胞系培养在体外四维肺模型的脱细胞肺基质中,以确定它们是否能形成原发性肿瘤,以及它们在多大程度上模拟人类肿瘤的组织学和特征。
获取大鼠肺脏,进行脱细胞处理后置于生物反应器中。为研究原发性肿瘤生长,我们通过气管将人乳腺癌细胞SUM159、MCF7或MDMB231接种到肺脏,并向肺动脉灌注含氧培养基。进行肺叶切除术,并对组织进行苏木精-伊红染色、Ki-67、半胱天冬酶-3、雌激素受体和孕激素受体抗体检测。
所有三种细胞系均在体外四维模型中生长,并形成了可灌注的肿瘤结节,其组织学和形态学与原发性肿瘤相似。SUM159和MDAMB231的增殖和凋亡指数高于MCF7。此外,MCF7保持其雌激素受体和孕激素受体阳性,而SUM159和MDAMB 231没有任何染色。
总体而言,我们的研究表明,人乳腺癌细胞可以在体外四维肺模型上生长,进而形成模拟原始肿瘤形态和组织学的原发性肿瘤结节。