Loss of E-cadherin, a molecule that mediates cell-cell adhesion, leads to an aggressive and metastatic form of breast cancer, i.e. Invasive Lobular Carcinoma (ILC). The aggressive cells are able to metastasize, because they have attained the capacity to sustain survival and induce blood vessel formation at their novel habitat. These are the conclusions of a study conducted at the Netherlands Cancer Institute by drs. Derksen and Jonkers, which will be published the November issue of the scientific journal Cancer Cell.
Glue
ILC accounts for 10-15% of all breast cancers. Although loss of E-cadherin –the glue that keeps cells together- has already been implicated in playing a role in ILC for more than 15 years, evidence to substantiate this potential role has been lacking. Now, researchers show that loss of E-cadherin is the driving force that initiates the development and progression of this disease.
A mouse model was constructed in which the E-cadherin gene was inactivated in specific cells of the mammary gland. The development of such a model is a very complex genetic experiment which consumes several years of research. In this setting, loss of E-cadherin not only induced invasiveness of mouse breast cancer cells; it also conferred potent survival capabilities. When normal cells are deprived of contacts within their natural environment, they will receive a signal which triggers programmed cell death. In contrast, the E-cadherin negative breast cancer cells were able to ignore this command and survive. More over, the breast cancer cells were shown to produce factors that stimulate the formation of new blood vessels. Tumors are dependent on blood vessel formation for the supply of oxygen and nutrients.
ILC in mice and man
Cancer progression and metastatic spread in mouse ILC shows noticeable similarities when compared to the development of human ILC. These findings emphasize the importance of this research, which is sponsored by grants from the Dutch Cancer Society (KWF) and Netherlands Organization for Scientific Research (NWO).
Patrick Derksen: ”ILCs are notoriously resistant to chemotherapy. Now that we have identified an initiating event that causes this type of cancer, we can use our mouse model to explore novel treatment strategies. We believe that ILC cells are able to metastasize, because of their intrinsic capacity to survive in unknown territory. The next challenging step will be to unravel the mechanism that controls this ability.”