The investigator's found that the "growth factors" did not promote cellular growth, which by itself is not a novel finding. It has long been appreciated that EGF-related factors are also important in other cellular activities such as cellular survival. Filardo and the research team, however, found that estrogen action through GPR30 had a more profound effect on tumor cell survival. They found that GPR30 promoted the assembly of what is called a "provisional extracellular matrix" -- a crucial event in cellular survival. More specifically, they found that release of growth factor by GPR30 required the activation of a latent adhesion receptor (known as integrin 51).
Filardo says, "Activation of integrin 51 by GPR30 is a significant event because it provides a way for invading cells to gain hold once they metastasize to tissues distant to the primary breast cancer. This happens because activated integrin 51 can convert soluble plasma protein fibronectin into an insoluble cage. The breast cancer cells can use this to adapt to a new environment."
In general, about two-thirds of all breast cancer cases involve tumors that retain expression of estrogen receptors (ER). They are presumed to proliferate in response to estrogen produced by the patient. Consequently, patients with ER-positive tumors receive hormonal agents (known as ER antagonists) that act by blocking the proliferative effects of estrogen promoted by the ER. As a result, the capacity of breast cancers to grow is reduced. The development of new drugs targeting GPR30 may be an important step in controlling breast cancer because this newly appreciated estrogen receptor is not promoting estrogen-dependent growth but may be critical in promoting breast tumor cell survival.
Filardo says, "There has been a recent shift toward treating ER-positive breast tumor patients with aromatase inhibitors such as tamoxifen that block estrogen biosynthesis. The thought is that this is yet another way to prevent estrogen from acting as its sole receptor, the ER." He concludes, "The discovery that GPR30 represents yet another estrogen receptor with biological significance for breast cancer furthers the argument that aromatase inhibitors would effectively block estrogen action at both types of estrogen receptors."