Fig. 5
From: CRIPTO antagonist ALK4L75A-Fc inhibits breast cancer cell plasticity and adaptation to stress
ALK4L75A-Fc reduces aggressive breast cancer cell phenotypes and proliferation of stressed cancer cells in vivo. a Expression changes in select stem cell, cancer stem cell, and EMT/MET associated transcripts in a contralateral pair of mock and ALK4L75A-Fc MDA-MB-231 tumors following 96 h of in vivo doxycycline treatment. b Representative images of mock and ALK4L75A-Fc-expressing MDA-MB-231 xenografts (n = 3 of each type). H&E, hematoxylin/eosin staining. E-Cadherin at the periphery of advanced tumors (2nd column). d = mammary duct. MKI67 staining of tumors in highly cellular areas and adjacent to acellular regions, A (right 4 panels). Scale = 250 μM. c Representative images of the overlap of MKI67 (green) and HIF1a (red) staining in MDA-MB-468 tumor sections with and without ALK4L75A-Fc expression. Four classes of cells could be identified, I–IV. d Blinded quantification of the four cell classes indicated in c across a set of 12 images (7 mock and 5 ALK4L75A-Fc) collected from 2 MDA-MB-468 mock and 2 MDA-MB-468 ALK4L75A-Fc tumors. *p < 0.05; Student’s t test. e Representative (n = 2) costaining for CRIPTO (green), GRP78 (red), phalloidin (blue), and DAPI (gray). Bracket = acellular region-adjacent CRIPTO staining cells. Scale bars = 100 μM (i) and 25 μM (ii), insets show colocalization of CRIPTO and GRP78 (yellow) at the cell periphery in bracketed regions