Heterogeneity of PD-L1 levels could indicate intra-tumoral or intra-patient heterogeneity, as each of these patients had multiple metastatic sites and the CTCs could break off from any or multiple of these sites.
Our findings showed incremented expression of multiple growth factors, pro-angiogenic /lymphangiogenic factors, metalloproteinases, chemokines and pro-inflammatory cytokines potentially relevant to the metastatic steps such as autocrine growth control, migration, interaction with stromal cells, angiogenesis, lymphangiogenesis and invasion.
Fig. 4 Multiple metastatic gastric polyps.
Multiple metastatic brain tumors and multifocal primary brain tumors of a single histological type are well described in the literature.
bPatients could have had multiple metastatic locations.
Treatment with anti-NCSTN mAbs impinged not only on cancer cell proliferation, but also on the multiple, crucial steps of the metastatic cascade: (i) the invasive potential, (ii) ability of cancer cells to degrade ECM via invadopodia extension, as well as (iii) trans-endothelial extravasation efficiency, were all inhibited.
Although diffuse type is not characterized by the multiple proceeding steps, this shows more metastatic phenotype with poorer prognosis.
Moreover, HIF signaling in malignant cells influences multiple steps within the metastatic cascade.
Despite the parts played by ubiquitin modifiers, removal of ubiquitin from the functional proteins by the deubiquitinating enzymes (DUBs) plays an important role in governing the multiple steps of the metastatic cascade, including local invasion, dissemination, and eventual colonization of the tumor to distant organs.
These 4 genes contribute to multiple steps of the metastatic process, such as endothelial tight junction (Le Jan et al., 2003), cell migration and invasion (Birkedal-Hansen et al., 1993; Howe et al., 2005), cell differentiation and colonization (Oskarsson et al., 2011).
