Sflomos George, Schaumann Nora, Christgen Matthias, Christgen Henriette, Bartels Stephan, Kreipe Hans, Battista Laura, Brisken Cathrin
ISREC-Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland.
Institute of Pathology, Hannover Medical School, Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
Cancers (Basel). 2023 Jun 22;15(13):3299. doi: 10.3390/cancers15133299.
Invasive lobular carcinoma (ILC) is a common breast cancer subtype that is often diagnosed at advanced stages and causes significant morbidity. Late-onset secondary tumor recurrence affects up to 30% of ILC patients, posing a therapeutic challenge if resistance to systemic therapy develops. Nonetheless, there is a lack of preclinical models for ILC, and the current models do not accurately reproduce the complete range of the disease. We created clinically relevant metastatic xenografts to address this gap by grafting the triple-negative IPH-926 cell line into mouse milk ducts. The resulting intraductal xenografts accurately recapitulate lobular carcinoma in situ (LCIS), invasive lobular carcinoma, and metastatic ILC in relevant organs. Using a panel of 15 clinical markers, we characterized the intratumoral heterogeneity of primary and metastatic lesions. Interestingly, intraductal IPH-926 xenografts express low but actionable HER2 and are not dependent on supplementation with the ovarian hormone estradiol for their growth. This model provides a valuable tool to test the efficiency of potential new ILC therapeutics, and it may help detect vulnerabilities within ILC that can be exploited for therapeutic targeting.
浸润性小叶癌（ILC）是一种常见的乳腺癌亚型，通常在晚期被诊断出来，会导致严重的发病率。晚期继发性肿瘤复发影响高达30%的ILC患者，如果对全身治疗产生耐药性，将构成治疗挑战。尽管如此，目前缺乏针对ILC的临床前模型，现有的模型也无法准确重现该疾病的全貌。我们通过将三阴性IPH - 926细胞系移植到小鼠乳腺导管中，创建了与临床相关的转移性异种移植模型，以填补这一空白。由此产生的导管内异种移植模型准确地再现了原位小叶癌（LCIS）、浸润性小叶癌以及相关器官中的转移性ILC。我们使用一组15种临床标志物，对原发性和转移性病变的肿瘤内异质性进行了表征。有趣的是，导管内IPH - 926异种移植瘤表达水平较低但可靶向治疗的HER2，并且其生长不依赖于卵巢激素雌二醇的补充。该模型为测试潜在的新型ILC治疗方法的有效性提供了有价值的工具，并且可能有助于发现ILC中可用于治疗靶向的薄弱环节。
