TFPI2 Promotes Perivascular Migration in an Angiotropism Model of Melanoma

Mo, Jing; Zhao, Xiulan; Wang, Wei; Zhao, Nan; Dong, Xueyi; Zhang, Yanhui; Cheng, Run-Fen; Sun, Baocun

doi:10.3389/fonc.2021.662434

Cited by 9 publications

(4 citation statements)

References 61 publications

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“…Knockdown of Ras-related associated with diabetes (RRAD), a GTPase commonly implicated in metabolic function and hepatocellular carcinomas, suppressed cancer cell invasion, proliferation, and EMT [ 66 , 67 ]. Finally, tissue factor pathway inhibitor 2 (TFPI2) has been shown to promote cancer metastasis through increased perivascular migration and ERK signaling [ 68 , 69 ].…”

Section: Discussionmentioning

confidence: 99%

Propagated Circulating Tumor Cells Uncover the Potential Role of NFκB, EMT, and TGFβ Signaling Pathways and COP1 in Metastasis

Jian-yun

Sharma

Arab

et al. 2023

Cancers

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Circulating tumor cells (CTCs), a population of cancer cells that represent the seeds of metastatic nodules, are a promising model system for studying metastasis. However, the expansion of patient-derived CTCs ex vivo is challenging and dependent on the collection of high numbers of CTCs, which are ultra-rare. Here we report the development of a combined CTC and cultured CTC-derived xenograft (CDX) platform for expanding and studying patient-derived CTCs from metastatic colon, lung, and pancreatic cancers. The propagated CTCs yielded a highly aggressive population of cells that could be used to routinely and robustly establish primary tumors and metastatic lesions in CDXs. Differential gene analysis of the resultant CTC models emphasized a role for NF-κB, EMT, and TGFβ signaling as pan-cancer signaling pathways involved in metastasis. Furthermore, metastatic CTCs were identified through a prospective five-gene signature (BCAR1, COL1A1, IGSF3, RRAD, and TFPI2). Whole-exome sequencing of CDX models and metastases further identified mutations in constitutive photomorphogenesis protein 1 (COP1) as a potential driver of metastasis. These findings illustrate the utility of the combined patient-derived CTC model and provide a glimpse of the promise of CTCs in identifying drivers of cancer metastasis.

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Section: Discussionmentioning

confidence: 99%

Propagated Circulating Tumor Cells Uncover the Potential Role of NFκB, EMT, and TGFβ Signaling Pathways and COP1 in Metastasis

Jian-yun

Sharma

Arab

et al. 2023

Cancers

View full text Add to dashboard Cite

show abstract

“…Knockdown of Ras-related associated with diabetes (RRAD), a GTPase commonly implicated in metabolic function and hepatocellular carcinomas, suppressed cancer cell invasion, proliferation, and EMT 63, 64 . Finally, tissue factor pathway inhibitor 2 (TFPI2) has been shown to promote cancer metastasis through increased perivascular migration and ERK signaling 65, 66 .…”

Section: Discussionmentioning

confidence: 99%

Propagated circulating tumor cells uncovers the role of NFκB and COP1 in metastasis

Jian-yun

Sharma

Arab

et al. 2022

Preprint

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Circulating tumor cells (CTCs), a population of cancer cells that represents the seeds of metastatic nodules, are a promising model system for studying metastasis. However, expansion of patient-derived CTCs ex vivo is challenging and dependent on the collection of high numbers of CTCs, which are ultra-rare. Here, we report the development of a combined CTC and CTC-derived xenograft (CDX) platform for expanding and studying patient-derived CTCs from metastatic colon, lung, and pancreatic cancers. Propagated CTCs yielded a highly aggressive population of cells that could be used to routinely and robustly establish primary tumors and metastatic lesions in CDXs. Differential gene analysis of the resultant CTC models emphasized a role for NF-kB signaling as a pan-cancer signaling pathway involved in metastasis. Furthermore, metastatic CTCs were identified through a prospective 5-gene signature (BCAR1, COL1A1, IGSF3, RRAD, and TFPI2). Whole-exome sequencing of CDX models and metastases further identified mutations in constitutive photomorphogenesis protein 1 (COP1) as a potential driver of metastasis. These findings illustrate the utility of the combined patient-derived CTC model and provide a glimpse of the promise of CTCs in identifying drivers of cancer metastasis.

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“…Cell invasion and migration were examined using transwell assays and scratch wound healing assays as previously described ( 39 ). For transwell invasion/migration assays, 2x10 4 cells were plated in the upper chamber (Transwell chambers, 8 mm pore size, BD Biosciences) in serum-free culture medium with or without Matrigel matrix (BD Biosciences) on the inserts.…”

Section: Methodsmentioning

confidence: 99%

MIF promotes cell invasion by the LRP1-uPAR interaction in pancreatic cancer cells

et al. 2023

Self Cite

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IntroductionPancreatic ductal adenocarcinoma (PDAC) is characterized by high aggressiveness and a hypoxic tumour microenvironment. Macrophage migration inhibitory factor (MIF) is a hypoxia-related pleiotropic cytokine that plays important roles in cancer. However, its role in PDAC progression has not been fully elucidated.MethodsThe clinical significance of MIF and hypoxia inducible factor 1 subunit alpha (HIF1A) in PDAC was analysed using immunohistochemical staining on PDAC tissues and data from KM-Plotter database. Spatial distribution of MIF and HIF1A gene expression was visualized by spatial transcriptomics in PDAC cell xenografts. To monitor the role of MIF in PDAC cell malignancy, immunostaining, lentivirus shRNA, migration assays, flow cytometry, transcriptomics and in vivo tumorigenicity were performed.ResultsThe spatial distribution of MIF and HIF1A was highly correlated and that high MIF expression was associated with poor prognosis of PDAC patients. MIF knockdown impaired cell invasion, with a decrease in the expression of urokinase-type plasminogen activator receptor (uPAR). Although PLAUR transcript was not reduced, a uPAR endocytic receptor, low-density lipoprotein receptor–related protein 1 (LRP1), was upregulated at both the mRNA and protein levels after MIF knockdown. The LRP1 antagonist RAP restored uPAR expression and invasiveness. MIF attenuated the nuclear translocation of p53, a transcriptional regulator of LRP1. Furthermore, MIF downregulation blunted the growth of PDAC cell xenografts and inhibited cell proliferation under normoxia and hypoxia. Transcriptome analysis also provided evidence for the role of MIF in cancer-associated pathways.DiscussionWe demonstrate a novel link between the two pro-invasive agents MIF and uPAR and explain how MIF increases PDAC cell invasion capability. This finding provides a basis for therapeutic intervention of MIF in PDAC progression.

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TFPI2 Promotes Perivascular Migration in an Angiotropism Model of Melanoma

Cited by 9 publications

References 61 publications

Propagated Circulating Tumor Cells Uncover the Potential Role of NFκB, EMT, and TGFβ Signaling Pathways and COP1 in Metastasis

Propagated Circulating Tumor Cells Uncover the Potential Role of NFκB, EMT, and TGFβ Signaling Pathways and COP1 in Metastasis

Propagated circulating tumor cells uncovers the role of NFκB and COP1 in metastasis

MIF promotes cell invasion by the LRP1-uPAR interaction in pancreatic cancer cells

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