Hypoxia promotes vasculogenic mimicry formation by vascular endothelial growth factor A mediating epithelial‐mesenchymal transition in salivary adenoid cystic carcinoma

Feline oral squamous cell carcinoma (FOSCC) is an aggressive malignancy with invasive and metastatic behavior. It is poorly responsive to chemotherapy and radiation. Neoplastic epithelial-mesenchymal transition (EMT) portends highly malignant behavior and enhances resistance to therapy. In transitioning to a more malignant phenotype, carcinoma stem cells undergo transformation mediated by expression of proteins, endowing them with mesenchymal properties advantageous to cell survival. The goal of the current study was to identify proteins associated with EMT in FOSCC. This study documents protein expression patterns in 10 FOSCC biopsies and 3 FOSCC cell lines (SCCF1, SCCF2, SCCF3), compatible with an EMT phenotype. As markers of EMT, P-cadherin, N-cadherin, vimentin, nuclear transcription factors Twist and Snail, hypoxia inducible factor 1α (HIF-1α), programmed death ligand 1, and vascular endothelial growth factor D, as well as E-cadherin, were examined using immunohistochemistry, Western blot, and enzyme-linked immunosorbent assay. P-cadherin, Twist, HIF-1α, and programmed death ligand 1 were commonly expressed in biopsies and cell lines. N-cadherin, classically associated with EMT, was not highly expressed, and E-cadherin was coexpressed along with proteins characteristic of EMT in all specimens. Production of vascular endothelial growth factor A by cell lines, a process regulated by HIF-1α expression, was suppressed by the small-molecule inhibitor dasatinib. These data are consistent with EMT in FOSCC and shed light on cellular changes that could contribute to the aggressive behavior of FOSCC.

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Malignant Pleural Effusion and ascites Induce Epithelial-Mesenchymal Transition and Cancer Stem-like Cell Properties via the Vascular Endothelial Growth Factor (VEGF)/Phosphatidylinositol 3-Kinase (PI3K)/Akt/Mechanistic Target of Rapamycin (mTOR) Pathway

Journal of Biological Chemistry ◽

10.1074/jbc.m116.753236 ◽

2016 ◽

Vol 291 (52) ◽

pp. 26750-26761 ◽

Cited By ~ 11

Author(s):

Tao Yin ◽

Guoping Wang ◽

Sisi He ◽

Guobo Shen ◽

Chao Su ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Pleural Effusion ◽

Malignant Pleural Effusion ◽

Epithelial Mesenchymal Transition ◽

Vascular Endothelial ◽

Phosphatidylinositol 3 Kinase ◽

Mesenchymal Transition ◽

Mechanistic Target Of Rapamycin ◽

Endothelial Growth Factor

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Vascular endothelial growth factor (VEGF) and hypoxia inducible factor-1 alpha (HIF-1ɑ) in lacrimal gland Adenoid cystic carcinoma: Correlation with clinical outcome

Annals of Diagnostic Pathology ◽

10.1016/j.anndiagpath.2021.151846 ◽

2021 ◽

pp. 151846

Author(s):

Shahzan Anjum ◽

Seema Sen ◽

Kunzang Chosdol ◽

Sameer Bakhshi ◽

Seema Kashyap ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Clinical Outcome ◽

Adenoid Cystic Carcinoma ◽

Lacrimal Gland ◽

Hypoxia Inducible Factor ◽

Vascular Endothelial ◽

Hypoxia Inducible Factor 1 ◽

Adenoid Cystic ◽

Endothelial Growth Factor

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Endometrial Stromal Decidualization Responds Reversibly to Hormone Stimulation and Withdrawal

Endocrinology ◽

10.1210/en.2015-1942 ◽

2016 ◽

Vol 157 (6) ◽

pp. 2432-2446 ◽

Cited By ~ 34

Author(s):

Jie Yu ◽

Sarah L. Berga ◽

Erika B. Johnston-MacAnanny ◽

Neil Sidell ◽

Indrani C. Bagchi ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Gap Junctions ◽

Epithelial Mesenchymal Transition ◽

Morphological Changes ◽

Vascular Endothelial ◽

Ovulatory Cycle ◽

Cx43 Expression ◽

Mesenchymal Transition ◽

Endothelial Growth Factor

Human endometrial stromal decidualization is required for embryo receptivity, angiogenesis, and placentation. Previous studies from our laboratories established that connexin (Cx)-43 critically regulates endometrial stromal cell (ESC) differentiation, whereas gap junction blockade prevents it. The current study evaluated the plasticity of ESC morphology and Cx43 expression, as well as other biochemical markers of cell differentiation, in response to decidualizing hormones. Primary human ESC cultures were exposed to 10 nM estradiol, 100 nM progesterone, and 0.5 mM cAMP for up to 14 days, followed by hormone withdrawal for 14 days, mimicking a biphasic ovulatory cycle. Reversible differentiation was documented by characteristic changes in cell shape. Cx43 was reversibly up- and down-regulated after the estradiol, progesterone, and cAMP treatment and withdrawal, respectively, paralleled by fluctuations in prolactin, vascular endothelial growth factor, IL-11, and glycodelin secretion. Markers of mesenchymal-epithelial transition (MET), and its counterpart epithelial-mesenchymal transition, followed reciprocal patterns corresponding to the morphological changes. Incubation in the presence of 18α-glycyrrhetinic acid, an inhibitor of gap junctions, partially reversed the expression of decidualization and MET markers. In the absence of hormones, Cx43 overexpression promoted increases in vascular endothelial growth factor and IL-11 secretion, up-regulated MET markers, and reduced N-cadherin, an epithelial-mesenchymal transition marker. The combined results support the hypothesis that Cx43-containing gap junctions and endocrine factors cooperate to regulate selected biomarkers of stromal decidualization and MET and suggest roles for both phenomena in endometrial preparation for embryonic receptivity.

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Honokiol: A Review of Its Anticancer Potential and Mechanisms

Cancers ◽

10.3390/cancers12010048 ◽

2019 ◽

Vol 12 (1) ◽

pp. 48 ◽

Cited By ~ 10

Author(s):

Chon Phin Ong ◽

Wai Leong Lee ◽

Yin Quan Tang ◽

Wei Hsum Yap

Keyword(s):

Vascular Endothelial Growth Factor ◽

Natural Products ◽

Cell Migration ◽

Growth Factor ◽

Migration And Invasion ◽

Vascular Endothelial ◽

Mesenchymal Transition ◽

Chemical Structures ◽

Endothelial Growth Factor ◽

Promising Source

Cancer is characterised by uncontrolled cell division and abnormal cell growth, which is largely caused by a variety of gene mutations. There are continuous efforts being made to develop effective cancer treatments as resistance to current anticancer drugs has been on the rise. Natural products represent a promising source in the search for anticancer treatments as they possess unique chemical structures and combinations of compounds that may be effective against cancer with a minimal toxicity profile or few side effects compared to standard anticancer therapy. Extensive research on natural products has shown that bioactive natural compounds target multiple cellular processes and pathways involved in cancer progression. In this review, we discuss honokiol, a plant bioactive compound that originates mainly from the Magnolia species. Various studies have proven that honokiol exerts broad-range anticancer activity in vitro and in vivo by regulating numerous signalling pathways. These include induction of G0/G1 and G2/M cell cycle arrest (via the regulation of cyclin-dependent kinase (CDK) and cyclin proteins), epithelial–mesenchymal transition inhibition via the downregulation of mesenchymal markers and upregulation of epithelial markers. Additionally, honokiol possesses the capability to supress cell migration and invasion via the downregulation of several matrix-metalloproteinases (activation of 5′ AMP-activated protein kinase (AMPK) and KISS1/KISS1R signalling), inhibiting cell migration, invasion, and metastasis, as well as inducing anti-angiogenesis activity (via the down-regulation of vascular endothelial growth factor (VEGFR) and vascular endothelial growth factor (VEGF)). Combining these studies provides significant insights for the potential of honokiol to be a promising candidate natural compound for chemoprevention and treatment.

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HSP 27 associates with epithelial–mesenchymal transition, stemness and radioresistance of salivary adenoid cystic carcinoma

Journal of Cellular and Molecular Medicine ◽

10.1111/jcmm.13510 ◽

2018 ◽

Vol 22 (4) ◽

pp. 2283-2298 ◽

Cited By ~ 11

Author(s):

Wei Chen ◽

Xiaohua Ren ◽

Jiashun Wu ◽

Xiaolei Gao ◽

Xiao Cen ◽

...

Keyword(s):

Adenoid Cystic Carcinoma ◽

Epithelial Mesenchymal Transition ◽

Salivary Adenoid Cystic Carcinoma ◽

Mesenchymal Transition ◽

Hsp 27 ◽

Adenoid Cystic

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Claudin-7 Inhibits Proliferation and Metastasis in Salivary Adenoid Cystic Carcinoma Through Wnt/β-Catenin Signaling

Cell Transplantation ◽

10.1177/0963689720943583 ◽

2020 ◽

Vol 29 ◽

pp. 096368972094358

Author(s):

Huan Ji ◽

Xu Ding ◽

Wei Zhang ◽

Yang Zheng ◽

Hongming Du ◽

...

Keyword(s):

Adenoid Cystic Carcinoma ◽

Epithelial Mesenchymal Transition ◽

Tumor Formation ◽

Biological Behavior ◽

Migration And Invasion ◽

Salivary Adenoid Cystic Carcinoma ◽

Mesenchymal Transition ◽

Adenoid Cystic ◽

Proliferation And Metastasis ◽

And Gender

The aim of this study was to investigate claudin-7 (CLDN7) expression in salivary adenoid cystic carcinoma (SACC) and its function in SACC cells. We determined CLDN7 expression in SACC tumors via immunohistochemistry and western blotting and evaluated the association between CLDN7 expression and clinicopathologic variables. Besides this, we constructed a stably transfected CLDN7 knockdown SACC-LM cell line via RNAi and assessed its biological behavior changes (cell viability, migration, and invasion). The correlation between CLDN7 and epithelial-mesenchymal transition (EMT) was analyzed. Additionally, a subcutaneous tumor formation model was used to assess SACC-LM cells tumorigenicity after the CLDN7 knockdown. In the present study, we found the CLDN7 expression of tumor group was lower than that in normal salivary glands and was significantly correlated with lymph node metastasis, recurrence, and gender. CLDN7 knockdown could add the proliferation and metastasis ability of SACC by regulating EMT through Wnt/β-catenin signaling pathway. In addition, CLDN7 knockdown in SACC promoted tumor growth in nude mice. CLDN7 inhibits cell proliferation and metastasis by inactivating the Wnt/β-catenin signaling in SACC. Thus, CLDN7 expression might be a useful marker to identify the potential for progression in SACC.

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