Anti-ITGA5 monoclonal antibody, clone 20G7

Breast cancer (BC) demonstrates considerable intratumoral morphological heterogeneity. The aim of this work was to evaluate the relationship among different morphological structures, the rate of metastasis, and efficacy of neoadjuvant chemotherapy (NAC) in NAC-treated (n = 427) and NAC-naive (n = 249) BC patients. We also studied the involvement of an epithelial-mesenchymal transition (EMT) in the development of the intratumoral morphological heterogeneity of BC. We found a significant association between the intratumoral morphological heterogeneity and the rate of BC metastasis and response to NAC, which, in most cases, correlated with the presence of alveolar and trabecular structures. In particular, the rate of lymph node metastasis in tumors containing alveolar and trabecular structures was higher compared to that in tumors lacking such structures. NAC-treated patients with alveolar and trabecular structures had a high distant metastasis rate and a low metastasis-free survival rate. Furthermore, alveolar and trabecular structures were found to be associated with a lack of response to NAC. Interestingly, the association between alveolar structures and a high distant metastasis rate was found only in NAC-unresponsive patients, whereas the association between trabecular structures and an increased distant metastasis was revealed in responders. Alveolar structures were associated with chemoresistance only in patients with lymph node metastases, whereas trabecular structures were associated with chemoresistance only in patients without lymph node metastases. In general, increased intratumoral morphological diversity correlated with considerable chemoresistance and a high metastasis rate of BC. We found variable expressions of epithelial (EPCAM and CDH1) and mesenchymal (ITGA5, ITGB5, CDH2, CDH11, TGFb2, ZEB1, MMP2, DCN, MST1R) markers and, thus, different EMT manifestations in different morphological structures. Therefore, intratumoral morphological heterogeneity of BC may serve as an indicator of the metastatic potential and tumor chemosensitivity.

Adsorption of proteins associating with their conformational changes plays crucial roles in regulating biomaterial-cell interactions and consequent tissue responses to implanted biomaterials. This study reports direct visualization of typical serum protein, vitronectin, one of the key adhesive proteins that participate in mediating cell behaviors, upon adsorption on typically designed surfaces. Carbon films with their surfaces being plasma grafted functional groups -COOH and -NH2 are used as the model substrata for this study. Negative-staining electron microscopy technique is employed for visualizing the adsorbed protein and 2D image classification is made and interpreted. Results show that adsorbed vitronectin tends to form multimer aggregate on the -COOH-grafted surfaces, exposing extensively its cell-binding RGD (arginineglycine-aspartic acid) motif for enhanced cell adhesion. The adsorbed vitronectin on the -NH2-grafted surface forms dimer aggregate with the binding sites being enwrapped. The -COOH-grafting triggers enhanced expressions of ITGA5, ITGAV, ITGB1, and ITGB3 of the adhered cells and this is likely attributed to the special spatial alignment of vitronectin upon adsorption. The conformational information of adsorbed vitronectin gained from the single particle electron micro-scopy analyses would shed light on design and construction of appropriate biomaterials surfaces for desired cellular behaviors.