\u27Normalizing\u27 the malignant phenotype of luminal breast cancer cells via alpha(v)beta(3)-integrin

Reestablishing tissue organization of breast cancer cells into acini was previously shown to override their malignant phenotype. In our study, we demonstrate that alpha(v)beta(3) integrin (Int-αvβ3), previously shown to play a role in cancer progression, promoted differentiation and growth arrest of organoids derived from luminal A breast cancer cells grown in their relevant three-dimensional microenvironment. These organoids differentiated into normal-like acini resembling a benign stage of breast tissue. Likewise, we demonstrate that Int-αvβ3 is selectively expressed in the epithelium of the benign stage of breast tissues, and is lost during the early stages of luminal A breast cancer progression. Notably, the organoids’ reversion into normal-like acini was mediated by cancer luminal progenitor-like cells expressing both EpCAM$^{high}$CD49f$^{low}$CD24$^{+}$ and Int-αvβ3. Furthermore, downregulation of Notch4 expression and downstream signaling was shown to mediate Int-αvβ3-induced reversion. Intriguingly, when luminal A breast cancer cells expressing Int-αvβ3 were injected into a humanized mouse model, differentiated tumors developed when compared with that generated by control cells. Hence, our data suggest that promoting differentiation of luminal A breast cancer cells by signaling emanating from Int-αvβ3 can potentially promote ‘normalization’ of their malignant phenotype and may prevent the malignant cells from progressing

Between political rhetoric and realpolitik calculations: Western diplomacy and the Baltic independence struggle in the Cold War endgame

Fifteen years after the Baltic SSRs' independence declarations, this article sheds new light on the Estonian, Latvian and Lithuanian struggle to regain statehood in the context of international relations between 1988 and 1991. Based on declassified archival sources from Western and Eastern archives, memoirs and official histories, it reveals the nature of 'Western' Baltic policies and analyses how (far) they impacted on the Soviet Union's demise. Second, the role universal normative values played in Western, Soviet and Baltic politics will be discussed in historical perspective; with the article concluding by offering some reflections on the general relationship between political rhetoric and foreign policy