Angiogenic Switching in the Alveolar Capillaries in Primary Lung Adenocarcinoma and Squamous Cell Carcinoma

Morishita, Chizuko; Jin, Enjing; Kikuchi, Mari; Egawa, Seiko; Fujiwara, Masakazu; Ohaki, Yoshiharu; Ghazizadeh, Mohammad; Takemura, Tamiko; Kawanami, Oichi

doi:10.1272/jnms.74.344

Cited by 10 publications

(10 citation statements)

References 19 publications

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“…oxygen supply and air space in the organ. the balance of proliferation and dormancy in orthotopic transplanted tumors may depend on how the tumor cells respond to the organ microenvironment (5)(6)(7)(15)(16)(17). the proliferation style in this orthotopic transplantation model may support the findings of Onn et al who found that paclitaxel had a different effect on human lung cancer cells growing orthotopically compared to those growing subcutaneously (3,18).…”

Section: Discussionsupporting

confidence: 74%

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Proliferation of human lung cancer in an orthotopic transplantation mouse model

Kang¹,

Omura²,

Suzuki³

et al. 2010

Experimental and Therapeutic Medicine

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Abstract. the objective of this study was to clarify the growth and proliferation style of human lung cancer grown in an orthotopic transplantation model. the human lung squamous cell carcinoma SQ5 and adenocarcinoma a549 cell lines were used. tumor cells suspended in serum-free medium were directly injected into the main bronchi of anesthetized female Balb/c athymic nude mice with simultaneous administration of 0.01 m ethylenediaminetetraacetic acid. Bromodeoxyuridine was injected into mice 20 min before sacrifice. Lung tissue with tumor nodules and subcutaneous tumors were fixed and confirmed by histological examinations. Bromodeoxyuridinelabeled cells in the tumor area were counted, and the proliferation index was calculated. lung tumor colonies of various sizes were obtained in the SQ5-and a549-cell orthotopically transplanted mice. Orthotopic SQ5 tumors whose minor diameter was 40-700 µm and major diameter was 80-830 µm showed no definite necrosis. Orthotopic SQ5 tumors whose minor diameter was 540-5,200 µm and major diameter was 600-6,100 µm showed definite necrosis in the tumor center. Similar results were also found in the orthotopic a549 tumors. the proliferation index was 7.38 (3.03)/10.63 (3.10) in the orthotopic SQ5 tumors with/without necrosis and 6.99 (2.10) in the subcutaneous SQ5 tumors with necrosis, respectively. the proliferation index was 2.70 (0.88)/3.53 (1.70) in the orthotopic a549 tumors with/without necrosis and 3.91 (0.63) in the subcutaneous a549 tumors with necrosis, respectively. the data suggest that this orthotopic transplantation model may provide the proper organ microenvironment for lung cancer growth and may be suitable for the target therapy research of human lung cancer.

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Section: Discussionsupporting

confidence: 74%

“…2 and 4) (8). These growth profiles are similar to those found in human squamous and adenocarcinoma lung tumor growth, respectively (15). this orthotopic transplantation model was considered to provide the proper organ microenvironment for lung cancer growth.…”

Section: Discussionsupporting

confidence: 67%

Proliferation of human lung cancer in an orthotopic transplantation mouse model

Kang¹,

Omura²,

Suzuki³

et al. 2010

Experimental and Therapeutic Medicine

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“…Glut 1 is a membrane factor facilitating glucose transport into the cell during conditions of hypoxia, initiating pathways of glucose metabolism (45). The correlation actually of this hypoxia-induced factor with squamous cell phenotype is another indication of the hypothesis that these tumors suffer more from hypoxia than adenocarcinomas (46,47). Thus, under hypoxic conditions, as indicated from Glut 1 expression, tumors producing adequate amounts of Beclin 1 seem to respond better to local environmental demands, as demonstrated by lack of necrosis.…”

Section: Discussionmentioning

confidence: 99%

Autophagy and Bcl‐2/BNIP3 death regulatory pathway in non‐small cell lung carcinomas

Karpathiou

Sivridis

Koukourakis

et al. 2012

APMIS

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We recently showed that non-small cell lung carcinomas (NSCLCs) are of dismal prognosis when encompassing accelerated autophagic activity. The regulation of this abnormally functioning degradation system and its association with hypoxia and apoptosis in lung carcinoma patients is unexplored. In this study we used 115 NSCLC tissues to examine the immunohistochemical expression of four distinct molecules - the major regulator of autophagy Beclin 1, the anti-apoptotic and anti-autophagic protein Bcl-2, the pro-apoptotic and pro-autophagic protein BNIP3, and a marker of hypoxia and glucolysis, the glucose transporter Glut 1. Most cases showed reduced reactivity for Beclin 1 (62%) and Bcl-2 (82%) proteins, almost half of our sample revealed strong BNIP3 expression (57%), whereas most of the carcinomas strongly expressed Glut 1 antigen (71%). Beclin 1 expression showed no association with survival. Bcl-2 positivity was a marker of good prognosis (p = 0.04), whereas BNIP3 (p = 0.0004) and Glut 1 (p = 0.03) expression correlated with poor outcome in Stage I disease. Autophagic status was negatively associated with Bcl-2 (p = 0.0006), but positively with Glut 1 expression (p = 0.001). In conclusion, the accelerated autophagic status in NSCLC is unrelated to Beclin 1 and BNIP3 expression, but does show significant association with Bcl-2 reactivity. Furthermore, we showed important correlations between glucolysis and autophagy, guiding new pathways in future lung carcinoma research.

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“…LACs often maintain glandular differentiation with acini, tubules, or papillary structures. Eventually, LAC cells which occlude the normal alveolar architecture invade into the alveolar interstitium and LACs often metastasize early [ 5 ]. Unfortunately, there is a lack of diagnostic and prognostic biomarkers to help guide therapeutic options in LAC.…”

Section: Introductionmentioning

confidence: 99%

GATA3-induced vWF upregulation in the lung adenocarcinoma vasculature

Pan

Liu

et al. 2017

Oncotarget

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Lung adenocarcinoma (LAC) is the leading cause of cancer-related death worldwide. Aberrant expression of genes expressed preferentially in the lung tumor vasculature may yield clues for prognosis and treatment. Von Willebrand factor (vWF) is a large multifunctional glycoprotein with a well-known function in hemostasis. However, vWF has been reported to exert an anti-tumor effect, independent of its role in hemostasis. We investigated the expression of vWF in LAC through immunohistochemical staining of tumor tissue microarrays (TMAs). We found that vWF was overexpressed preferentially in the tumor vasculature of LAC compared with the adjacent tissue vasculature. Consistently, elevated vWF expression was found in endothelial cells (ECs) of fresh human LAC tissues and transplanted mouse LAC tissues. To understand the mechanism underlying vWF up-regulation in LAC vessels, we established a co-culture system. In this system, conditioned media (CM) collected from A549 cells increased vWF expression in human umbilical vein endothelial cells (HUVECs), suggesting enhanced expression is regulated by the LAC secretome. Subsequent studies revealed that the transcription factor GATA3, but not ERG, a known regulator of vWF transcription in vascular cells, mediated the vWF elevation. Chromatin immunoprecipitation (ChIP) assays validated that GATA3 binds directly to the +220 GATA binding motif on the human vWF promoter and A549 conditioned media significantly increases the binding of GATA3. Taken together, we demonstrate that vWF expression in ECs of LAC is elevated by the cancer cell-derived secretome through enhanced GATA3-mediated transcription.

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Angiogenic Switching in the Alveolar Capillaries in Primary Lung Adenocarcinoma and Squamous Cell Carcinoma

Cited by 10 publications

References 19 publications

Proliferation of human lung cancer in an orthotopic transplantation mouse model

Proliferation of human lung cancer in an orthotopic transplantation mouse model

Autophagy and Bcl‐2/BNIP3 death regulatory pathway in non‐small cell lung carcinomas

GATA3-induced vWF upregulation in the lung adenocarcinoma vasculature

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