S100A10 Promotes Pancreatic Ductal Adenocarcinoma Cells Proliferation, Migration and Adhesion through JNK/LAMB3-LAMC2 Axis

Lin, Hai; Yang, Pengfei; Li, Bixiang; Chang, Yue; Chen, Yutong; Li, Yaning; Liu, Kecheng; Liang, Xinyue; Chen, Tianliang; Dai, Yalan; Pang, Wenzheng; Zeng, Linjuan

doi:10.3390/cancers15010202

Cited by 9 publications

(8 citation statements)

References 55 publications

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“…In addition, our results corroborate a previous MS‐based profiling that noticed decreased protein expression of PLOD3, GAPDH and LDHA in NCT as compared to treatment‐naïve PDAC 12 . A number of publications associated S100 proteins with tumor proliferation and poor survival in PDAC 30–32 . Depletion of proteins, which are often found overexpressed or associated with a dismal survival in PDAC, may generally indicate efficacy of neoadjuvant therapy and elucidate proteins, which are worth being studied as diagnostic biomarker.…”

Section: Resultssupporting

confidence: 88%

“…12 A number of publications associated S100 proteins with tumor proliferation and poor survival in PDAC. [30][31][32] Depletion of proteins, which are often found overexpressed or associated with a dismal survival in PDAC, may generally indicate efficacy of neoadjuvant therapy and elucidate proteins, which are worth being studied as diagnostic biomarker.…”

Section: Both Nct and Ncrt Yield Depletion Of Glycolytic Ecm S100 And...mentioning

confidence: 99%

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Neoadjuvant chemo‐ or chemo‐radiation‐therapy of pancreatic ductal adenocarcinoma differentially shift ECM composition, complement activation, energy metabolism and ribosomal proteins of the residual tumor mass

Stillger,

Kurowski,

Bronsert

et al. 2024

Intl Journal of Cancer

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Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer, often diagnosed at stages that dis‐qualify for surgical resection. Neoadjuvant therapies offer potential tumor regression and improved resectability. Although features of the tumor biology (e.g., molecular markers) may guide adjuvant therapy, biological alterations after neoadjuvant therapy remain largely unexplored. We performed mass spectrometry to characterize the proteomes of 67 PDAC resection specimens of patients who received either neoadjuvant chemo (NCT) or chemo‐radiation (NCRT) therapy. We employed data‐independent acquisition (DIA), yielding a proteome coverage in excess of 3500 proteins. Moreover, we successfully integrated two publicly available proteome datasets of treatment‐naïve PDAC to unravel proteome alterations in response to neoadjuvant therapy, highlighting the feasibility of this approach. We found highly distinguishable proteome profiles. Treatment‐naïve PDAC was characterized by enrichment of immunoglobulins, complement and extracellular matrix (ECM) proteins. Post‐NCT and post‐NCRT PDAC presented high abundance of ribosomal and metabolic proteins as compared to treatment‐naïve PDAC. Further analyses on patient survival and protein expression identified treatment‐specific prognostic candidates. We present the first proteomic characterization of the residual PDAC mass after NCT and NCRT, and potential protein candidate markers associated with overall survival. We conclude that residual PDAC exhibits fundamentally different proteome profiles as compared to treatment‐naïve PDAC, influenced by the type of neoadjuvant treatment. These findings may impact adjuvant or targeted therapy options.

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Section: Resultssupporting

confidence: 88%

Section: Both Nct and Ncrt Yield Depletion Of Glycolytic Ecm S100 And...mentioning

confidence: 99%

Neoadjuvant chemo‐ or chemo‐radiation‐therapy of pancreatic ductal adenocarcinoma differentially shift ECM composition, complement activation, energy metabolism and ribosomal proteins of the residual tumor mass

Stillger,

Kurowski,

Bronsert

et al. 2024

Intl Journal of Cancer

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“…Furthermore, laminins LAMBC2 and LAMB3 support cancer progression and resistance to gemcitabine -one of the main chemotherapeutics used in PDAC patients [61,62]. In general, the association with poor prognosis of the stroma signature is consistent with the one described in previous studies for each gene: CEACAM5 [63], CEACAM6 [64], FN1 [65], GJB2 [66], GPRC5A [67], LAMB3 [68,69], LAMC2 [68,69], SFN [70], SLC6A14 [71], TSPAN1 [72], VCAN [65]. The meta-analysis from transcriptomic studies allows a be er understanding of the PDAC environment.…”

Section: Discussionsupporting

confidence: 86%

A comprehensive transcriptional signature in pancreatic ductal adenocarcinoma reveals new insights into the immune and desmoplastic microenvironment

Pérez-Díez

Andreu

Hidalgo

et al. 2023

Preprint

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Pancreatic ductal adenocarcinoma (PDAC) prognosis and treatment response remains devastatingly poor due partly to the highly heterogeneous, aggressive, and immunosuppressive nature of this tumor type. The intricate relationship between stroma, inflammation, and immunity remains vaguely understood in the PDAC microenvironment. Here, we performed a meta-analysis of stroma-, and immune-related gene expression in the PDAC microenvironment to improve disease prognosis and therapeutic development. We selected twenty-one PDAC studies from the Gene Expression Omnibus and ArrayExpress databases, including 922 samples (320 controls and 602 cases). Differential gene enrichment analysis identified 1153 significant dysregulated genes in PDAC patients that contribute to a desmoplastic stroma and an immunosuppressive environment (the hallmarks of PDAC tumors). The results highlighted two gene signatures related to the immune and stromal environments that cluster PDAC patients in high- and low-risk groups, impacting patient stratification and therapeutic decision-making. Moreover, HCP5, SLFN13, IRF9, IFIT2, and IFI35 immune genes were related to prognosis value in PDAC patients, for the first time.

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“…Pharmacological inhibition of α‐enolase‐1 using an inhibitory antibody suppressed plasminogen‐dependent invasion of human PDAC cells, and their metastatic spreading in mice [ 52 ]. Moreover reduction of S100A10 in PANC‐1 reduced orthotopic tumor growth in mice [ 54 ]. Collectively, these findings indicate that linking plasmin(ogen) to the tumor cell surface through multiple receptors can promote PDAC tumor growth.…”

Section: Discussionmentioning

confidence: 99%

Plasminogen deficiency suppresses pancreatic ductal adenocarcinoma disease progression

Chowdhury,

Yang,

Dutta

et al. 2023

Molecular Oncology

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Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal metastatic disease associated with robust activation of the coagulation and fibrinolytic systems. However, the potential contribution of the primary fibrinolytic protease plasminogen to PDAC disease progression has remained largely undefined. Mice bearing C57Bl/6‐derived KPC (KRasG12D, TRP53R172H) tumors displayed evidence of plasmin activity in the form of high plasmin–antiplasmin complexes and high plasmin generation potential relative to mice without tumors. Notably, plasminogen‐deficient mice (Plg‐) had significantly diminished KPC tumor growth in subcutaneous and orthotopic implantation models. Moreover, the metastatic potential of KPC cells was significantly diminished in Plg‐ mice, which was linked to reduced early adhesion and/or survival of KPC tumor cells. The reduction in primary orthotopic KPC tumor growth in Plg‐ mice was associated with increased apoptosis, reduced accumulation of pro‐tumor immune cells, and increased local proinflammatory cytokine production. Elimination of fibrin(ogen), the primary proteolytic target of plasmin, did not alter KPC primary tumor growth and resulted in only a modest reduction in metastatic potential. In contrast, deficiencies in the plasminogen receptors Plg‐RKT or S100A10 in tumor cells significantly reduced tumor growth. Plg‐RKT reduction in tumor cells, but not reduced S100A10, suppressed metastatic potential in a manner that mimicked plasminogen deficiency. Finally, tumor growth was also reduced in NSG mice subcutaneously or orthotopically implanted with patient‐derived PDAC tumor cells in which circulating plasminogen was pharmacologically reduced. Collectively, these studies suggest that plasminogen promotes PDAC tumor growth and metastatic potential, in part through engaging plasminogen receptors on tumor cells.

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S100A10 Promotes Pancreatic Ductal Adenocarcinoma Cells Proliferation, Migration and Adhesion through JNK/LAMB3-LAMC2 Axis

Cited by 9 publications

References 55 publications

Neoadjuvant chemo‐ or chemo‐radiation‐therapy of pancreatic ductal adenocarcinoma differentially shift ECM composition, complement activation, energy metabolism and ribosomal proteins of the residual tumor mass

Neoadjuvant chemo‐ or chemo‐radiation‐therapy of pancreatic ductal adenocarcinoma differentially shift ECM composition, complement activation, energy metabolism and ribosomal proteins of the residual tumor mass

A comprehensive transcriptional signature in pancreatic ductal adenocarcinoma reveals new insights into the immune and desmoplastic microenvironment

Plasminogen deficiency suppresses pancreatic ductal adenocarcinoma disease progression

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