Behavior of metastatic and nonmetastatic breast tumors in old mice
Behavior of metastatic and nonmetastatic breast tumors in old mice
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DOI：
10.1177/153537020422900711
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发表时间：
2004-07-01
影响因子：
3.2
通讯作者：
Reddick, R
中科院分区：
文献类型：
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作者：
Gravekamp, C;Sypniewska, R;Reddick, R
乳腺癌的发病率和死亡率随着年龄的增长而增加。更好地了解老年受试者中转移性和非转移性乳腺肿瘤的生物学行为可能有助于开发更好的乳腺癌治疗方法。在这项研究中，我们使用同基因转移性（4 TO 7 cg）和非转移性（64 pT）小鼠乳腺肿瘤模型在三个年龄水平，以评估各种特征，被认为是重要的有效的抗乳腺癌免疫治疗。这些包括肿瘤大小和生长，转移，血管形成，原发性乳腺肿瘤和转移中肿瘤相关抗原（TAA）Mage-b（与人MAGE-B同源）的基因表达水平，以及肿瘤部位腹股沟淋巴结中CD 4（+）和CD 8（+）T细胞的存在。通过将小鼠乳腺肿瘤细胞系4 TO 7 cg或64 pT注射到正常3月龄、9月龄或21/24月龄BALB/c小鼠的乳腺脂肪垫中，产生原发性乳腺肿瘤和转移瘤。在非转移性乳腺肿瘤模型中，与年轻小鼠相比，在老年小鼠中观察到显著更小的肿瘤。这与腹股沟淋巴结中CD 8 + T细胞百分比的显著增加以及老年原发性肿瘤中Mage-b表达水平的显著升高相关。在转移性（4 TO 7 cg）乳腺肿瘤模型中，在老年小鼠中发现了不太明显、不具有统计学显著性的较小肿瘤尺寸，在CD 8（+）T细胞百分比或Mage-b表达水平方面没有差异。然而，在这个小鼠模型中，几乎所有的转移瘤都显示出高水平的Mage-b表达（比相同动物中的原发性肿瘤高2- 3倍），而与年龄无关。这些结果表明，转移性和非转移性乳腺肿瘤模型可能是有用的模型系统，以分析如何为人类乳腺癌疫苗可以定制老年。
Breast cancer incidence and mortality increase with age. A better understanding of the biological behavior of metastatic and nonmetastatic breast tumors in older subjects may help to develop improved breast cancer therapies. In this study, we used syngeneic metastatic (4TO7cg) and nonmetastatic (64pT) mouse breast tumor models at three age levels to evaluate various characteristics that are considered to be important for effective anti-breast cancer immunotherapy. These included tumor size and growth, metastases, vascularization, gene expression levels of the tumor-associated antigen (TAA) Mage-b (homologous to human MAGE-B) in primary breast tumors and metastases, and the presence of CD4(+) and CD8(+) T cells in the inguinal lymph nodes at the site of the tumor. The primary breast tumors and metastases were generated by injection of mouse mammary tumor cell lines 4TO7cg or 64pT into a mammary fat pad of normal 3-, 9-, or 21/24-month old BALB/c mice. In the nonmetastatic breast tumor model, significantly smaller tumors were observed in old compared with young mice. This was associated with a significant increase in the percentage of CD8+ T cells in inguinal lymph nodes and significantly higher Mage-b expression levels in the primary tumors at old age. In the metastatic (4TO7cg) breast tumor model, a less pronounced, not statistically significant, smaller tumor size was found in the old mice, without a difference in the percentage of CD8(+) T cells or Mage-b expression levels. However, in this mouse model almost all metastases showed high levels of Mage-b expression (2- to 3-fold higher than the primary tumors in the same animals) regardless of age. These results indicate that the metastatic and nonmetastatic breast tumor models could be useful model systems to analyze how breast cancer vaccines for humans can be tailored to old age.