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ALCAM: A Novel Surface marker on EpCAMlow Circulating Tumor Cells

ABSTRACT: Abstract: Background: Current strategies in circulating tumor cell (CTC) isolation in pancreatic cancer heavily rely on the EpCAM and cytokeratin cell status. EpCAM is generally not a good marker given its transitory change during EMT or TME. There is a need to identify other surface markers to capture the complete repertoire of PDAC CTCs. The primary objective is to charac-terize putative protein biomarkers on the CTCs’ surface expressing low or negligible levels of EpCAM to aid with the investigation of pancreatic cancer in patients with metastatic tumors. Methods: Flow cytometry and surface mass spectrometry was used to identify proteins ex-pressed on the surface of PDAC CTCs in culture. CTCs were grown under conditions of attach-ment and in co-culture with naïve neutrophils. Putative biomarkers were then validated in GEMMs and patient samples. Results: Surface proteomic profiling of CTCs identified several novel protein biomarkers. ALCAM was identified as a novel robust marker in GEMM models and in patient samples. Conclusions: We identified several novel surface biomarkers on CTCs expressed under differing conditions of culture among which, we validated expression of AL-CAM on patient CTCs.

ORGANISM(S): Homo sapiens (human)

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PROVIDER: S-BSST861 | bioimages |

REPOSITORIES: bioimages

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Project description:BackgroundProprotein convertase subtilisin/kexin type 9 (PCSK9), the last member of the proprotein convertase family, functions as a classic regulator of low-density lipoprotein (LDL) by interacting with low-density lipoprotein receptor (LDLR). Recent studies have shown that PCSK9 can affect the occurrence and development of tumors and can be used as a novel therapeutic target. However, a comprehensive pan-cancer analysis of PCSK9 has yet to be conducted.MethodsThe potential oncogenic effects of PCSK9 in 33 types of tumors were explored based on the datasets of The Cancer Genome Atlas (TCGA) dataset. In addition, the immune regulatory role of PCSK9 inhibition was evaluated via in vitro cell coculture and the tumor-bearing mouse model. Finally, the antitumor efficacy of targeted PCSK9 combined with OVA-II vaccines was verified.ResultsOur results indicated that PCSK9 was highly expressed in most tumor types and was significantly correlated with late disease stage and poor prognosis. Additionally, PCSK9 may regulate the tumor immune matrix score, immune cell infiltration, immune checkpoint expression, and major histocompatibility complex expression. Notably, we first found that dendritic cell (DC) infiltration and major histocompatibility complex-II (MHC-II) expression could be upregulated by PCSK9 inhibition and improve CD8+ T cell activation in the tumor immune microenvironment, thereby achieving potent tumor control. Combining PCSK9 inhibitors could enhance the efficacies of OVA-II tumor vaccine monotherapy.ConclusionsConclusively, our pan-cancer analysis provided a more comprehensive understanding of the oncogenic and immunoregulatory roles of PCSK9 and demonstrated that targeting PCSK9 could increase the efficacy of long peptide vaccines by upregulating DC infiltration and MHC-II expression on the surface of tumor cells. This study reveals the critical oncogenic and immunoregulatory roles of PCSK9 in various tumors and shows the promise of PCSK9 as a potent immunotherapy target.

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ALCAM: A Novel Surface marker on EpCAMlow Circulating Tumor Cells

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