Downregulation of Hepatoma-Derived Growth Factor Contributes to Retarded Lung Metastasis via Inhibition of Epithelial–Mesenchymal Transition by Systemic POMC Gene Delivery in Melanoma

Tsai, Han-En; Liu, Guei‐Sheung; Kung, Mei-Lang; Liu, Lifeng; Wu, Jian-Ching; Tang, Chia-Hua; Huang, C. C.; Chen, San-Cher; Lam, Hing‐Chung; Wu, Chieh‐Shan; Tai, Ming‐Hong

doi:10.1158/1535-7163.mct-12-0832

Cited by 26 publications

(15 citation statements)

References 40 publications

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“…This binding defect was even more pronounced when cryo MSCs were exposed to vascular flow conditions. Specifically, by utilizing a three-dimensional endothelialized fluidic system (Tsai et al., 2013; Figure 1F), we infused cryo and live MSCs at a rate equivalent to 2 dynes/cm 2 into the microfluidic device for 1 hr and observed a profound difference in the ability of Cyro MSCs to bind to endothelial cells compared with live MSCs (live MSCs 6.3 ± 0.9/channel versus cryo MSCs 1.3 ± 0.3/channel; Figure 1G).…”

Section: Resultsmentioning

confidence: 99%

Actin Cytoskeletal Disruption following Cryopreservation Alters the Biodistribution of Human Mesenchymal Stromal Cells In Vivo

Chinnadurai¹,

Garcia²,

Sakurai³

et al. 2014

Stem Cell Reports

122

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SummaryMesenchymal stromal cells have shown clinical promise; however, variations in treatment responses are an ongoing concern. We previously demonstrated that MSCs are functionally stunned after thawing. Here, we investigated whether this cryopreservation/thawing defect also impacts the postinfusion biodistribution properties of MSCs. Under both static and physiologic flow, compared with live MSCs in active culture, MSCs thawed from cryopreservation bound poorly to fibronectin (40% reduction) and human endothelial cells (80% reduction), respectively. This reduction correlated with a reduced cytoskeletal F-actin content in post-thaw MSCs (60% reduction). In vivo, live human MSCs could be detected in murine lung tissues for up to 24 hr, whereas thawed MSCs were undetectable. Similarly, live MSCs whose actin cytoskeleton was chemically disrupted were undetectable at 24 hr postinfusion. Our data suggest that post-thaw cryopreserved MSCs are distinct from live MSCs. This distinction could significantly affect the utility of MSCs as a cellular therapeutic.

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Section: Resultsmentioning

confidence: 99%

Actin Cytoskeletal Disruption following Cryopreservation Alters the Biodistribution of Human Mesenchymal Stromal Cells In Vivo

Chinnadurai¹,

Garcia²,

Sakurai³

et al. 2014

Stem Cell Reports

122

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“…HDGF overexpression has been associated with lymph node metastasis, stimulation of breast cancer cell invasiveness and to promote EMT by upregulation of vimentin . Conversely, downregulation of HDGF suppressed lung metastasis and EMT in malignant melanoma .…”

Section: Discussionmentioning

confidence: 99%

Quantitative proteomics of fractionated membrane and lumen exosome proteins from isogenic metastatic and nonmetastatic bladder cancer cells reveal differential expression of EMT factors

et al. 2014

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Cancer cells secrete soluble factors and various extracellular vesicles, including exosomes, into their tissue microenvironment. The secretion of exosomes is speculated to facilitate local invasion and metastatic spread. Here, we used an in vivo metastasis model of human bladder carcinoma cell line T24 without metastatic capacity and its two isogenic derivate cell lines SLT4 and FL3, which form metastases in the lungs and liver of mice, respectively. Cultivation in CLAD1000 bioreactors rather than conventional culture flasks resulted in a 13- to 16-fold increased exosome yield and facilitated quantitative proteomics of fractionated exosomes. Exosomes from T24, SLT4, and FL3 cells were partitioned into membrane and luminal fractions and changes in protein abundance related to the gain of metastatic capacity were identified by quantitative iTRAQ proteomics. We identified several proteins linked to epithelial-mesenchymal transition, including increased abundance of vimentin and hepatoma-derived growth factor in the membrane, and casein kinase II α and annexin A2 in the lumen of exosomes, respectively, from metastatic cells. The change in exosome protein abundance correlated little, although significant for FL3 versus T24, with changes in cellular mRNA expression. Our proteomic approach may help identification of proteins in the membrane and lumen of exosomes potentially involved in the metastatic process.

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“…HDGF is known to play an important role in vascular growth and formation by regulating endothelial cell proliferation and migration [17, 18]. Thus, HDGF derived from tumors may promote tumor growth and angiogenesis via paracrine mechanisms.…”

Section: Discussionmentioning

confidence: 99%

High Nuclear Expression of HDGF Correlates with Disease Progression and Poor Prognosis in Human Endometrial Carcinoma

et al. 2014

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Aims. This study examined the correlation between high nuclear expression of hepatoma-derived growth factor (HDGF) and clinicopathologic data in endometrial carcinoma (EC), including patient survival. Methods. One hundred and twenty-two endometrial carcinoma (EC) patients from 2002 to 2008 were reviewed in the study. HDGF expression in tumor tissues was examined using immunohistochemistry (IHC), and its association with clinicopathological parameters was evaluated. Tumors with 80% or more nuclei staining were regarded as high expression and tumors with less than 80% nuclei staining considered as low expression. Results and Conclusions. Immunohistochemical analysis revealed that HDGF was expressed in both the nucleus and cytoplasm. High nuclear expression of HDGF was positively correlated with FIGO stage (P = 0.032), but not associated with other clinical features, such as histological grading or lymph node status. Patients with high expression of HDGF had poorer overall survival rates than those with low expression of HDGF (P = 0.001). However, multivariate analyses showed that high nuclear expression of HDGF protein was not an independent predictor of prognosis for EC patients (P = 0.111). Our results suggest that high nuclear expression of HDGF is a potential unfavorable factor for the progression and prognosis of EC.

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Downregulation of Hepatoma-Derived Growth Factor Contributes to Retarded Lung Metastasis via Inhibition of Epithelial–Mesenchymal Transition by Systemic POMC Gene Delivery in Melanoma

Cited by 26 publications

References 40 publications

Actin Cytoskeletal Disruption following Cryopreservation Alters the Biodistribution of Human Mesenchymal Stromal Cells In Vivo

Actin Cytoskeletal Disruption following Cryopreservation Alters the Biodistribution of Human Mesenchymal Stromal Cells In Vivo

Quantitative proteomics of fractionated membrane and lumen exosome proteins from isogenic metastatic and nonmetastatic bladder cancer cells reveal differential expression of EMT factors

High Nuclear Expression of HDGF Correlates with Disease Progression and Poor Prognosis in Human Endometrial Carcinoma

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