Invasive lobular carcinoma (ILC) is breast cancer that begins in one of the glands that make milk, called lobules. More than 90% of ILC tumors also contain estrogen receptors, meaning that they can receive hormone signals from the body, e.g., estradiol, that can spur their growth and metastasis.
As compared to other breast cancers, ILC is relatively understudied. The reason is the lower incidence of ILC in general and because ILC tumors don’t lend themselves to growth in culture.
Now, scientists at EPFL‘s have successfully overcome the limitations of ILC and have developed a xenograft model that simulates the tumor with high accuracy. Scientists grafted two ILC-derived metastatic breast cancer cell lines and freshly resected ILC tumors from patients directly into the milk ducts of mice that are immune deficient.
This approach allowed them to develop a series of in vivo models of lobular breast cancer.
George Sflomos, the first author of the study, said, “The samples preserve the histomorphological aspects and the peculiar metastatic patterns of ILC. The findings are particularly important for studying ILC metastasis which is primarily responsible for ILC cancer-related mortality.”
The model tumors likewise uncovered a few privileged insights into ILC biology. They seem to have similar peculiarities in the extracellular matrix-like their intrinsic capacity to create elastin, collagens, and the collagen-modifying enzyme LOXL1. Thus, when the scientists hindered all LOX enzymes, they saw a decrease in essential tumor growth, metastasis, and estrogen receptor signaling.
Sflomos said, “LOXL1 proved essential for in vivo tumor progression, which suggests that targeting the ILC tumor’s microenvironment can be a promising therapeutic approach that opens up new horizons on the biology of the disease that would benefit ILC patients.”
Professor Cathrin Brisken said, “This model provides us with the first in‐depth insights into the most common breast cancer special types estrogen receptor-positive breast cancer subtype. This experimental modeling of ILC will help identify molecular mechanisms specific to the disease and discover new therapeutic targets soon.”
- George Sflomos et al. Intraductal xenografts show lobular carcinoma cells rely on their extracellular matrix and LOXL1. EMBO Molecular Medicine 22 February 2021. DOI: 10.15252/emmm.202013180