Surface PD-L1, E-cadherin, CD24, and VEGFR2 as markers of epithelial cancer stem cells associated with rapid tumorigenesis

Abstract

Cancer cells require both migratory and tumorigenic property to establish metastatic tumors outside the primary microenvironment. Identifying the characteristic features of migratory cancer stem cells with tumorigenic property is important to predict patient prognosis and combat metastasis. Here we established one epithelial and two mesenchymal cell lines from ascites of a bladder cancer patient (i.e. cells already migrated outside primary tumor). Analyses of these cell lines demonstrated that the epithelial cells with surface expression of PD-L1, E-cadherin, CD24, and VEGFR2 rapidly formed tumors outside the primary tumor microenvironment in nude mice, exhibited signatures of immune evasion, increased stemness, increased calcium signaling, transformation, and novel E-cadherin–RalBP1 interaction. The mesenchymal cells on the other hand, exhibited constitutive TGF-β signaling and were less tumorigenic. Hence, targeting epithelial cancer stem cells with rapid tumorigenesis signatures in future might help to combat metastasis.

An effective dendritic cell‐based vaccine containing glioma stem‐like cell lysate and CpG adjuvant for an orthotopic mouse model of glioma

“…GSCs are the most important target for glioma therapy. The present results indicate that PD‐L1 was upregulated in GL261‐derived neurospheres rather than in conventionally cultured GL261 cells, concurrent with previous reports …”

“…Several studies have analyzed PD-L1 expression in CSCs. [33][34][35] In the present study, flow cytometry analysis revealed that PD-L1 expression was greater in GL261-derived neurospheres than in GL261 cells (Fig. 4d).…”

“…The present results indicate that PD-L1 was upregulated in GL261-derived neurospheres rather than in conventionally cultured GL261 cells, concurrent with previous reports. 33,34 Combining negative immune regulation of the PD-1/PD-L1 pathway and PD-1/PD-L1 upregulation upon STDEN-VANT administration, we hypothesized that PD-L1 blockade might interrupt immunosuppression and promote anti-tumor activity of effector T cells. Our hypothesis was substantiated in the orthotopic glioma mouse model, wherein addition of anti-PD-L1 mAb to STDENVANT enhanced the therapeutic potency of the therapy, albeit with nonsignificant differences in brain-infiltrating and LN-resident IFN-γ-producing CD8 + T cell densities, although there was a weak increasing trend upon combinatorial treatment.…”

Tumor-Intrinsic PD-L1 Signaling in Cancer Initiation, Development and Treatment: Beyond Immune Evasion

“…Interestingly, a link between PD-L1 expression and EMT/CSC-like phenotypes has been reported. For example, bladder cancer cells with surface expression of PD-L1 exhibited signatures of immune evasion as well as increased stemness ( 93 ). PD-L1 has been shown to be preferentially expressed on CD44 high CSCs in lung cancer cells ( 94 ).…”

<p>Clinical Outcomes and Safety of Apatinib Mesylate in the Treatment of Advanced Non-Squamous Non-Small Cell Lung Cancer in Patients Who Progressed After Standard Therapy and Analysis of the <em>KDR</em> Gene Polymorphism</p>

“…37 It has been shown that high levels of KDR expression in tumor cells facilitate the regeneration of blood vessels, increasing the risk of relapse and metastasis. 38,39 Some research studies showed that high expression of the KDR gene was associated with worse PFS and OS in patients with NSCLC 40 and cervical cancer. 41 These findings are consistent, to some extent, with those of our study.…”