Hypoxic regulation and prognostic value of LAMP3 expression in breast cancer

Nagelkerke, Anika; Mujčić, Hilda; Bussink, Johan; Wouters, Bradly G.; Laarhoven, Hanneke W. M. van; Sweep, Fred C.G.J.; Span, Paul N.

doi:10.1002/cncr.25938

Cited by 61 publications

(79 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The pattern of upregulated expression of Lamp3, PLD, and eNOS and decreased expression of SPARC is characteristic of cancer cell growth and metastasis. 48,49,51,67,68 Treating rats from the start of the SuHx protocol with MAZ51 ameliorated the developed PH and significantly reduced the number of obliterated pulmonary arterioles (Fig. 5), indicating to us that the elevated tissue levels of the isoforms VEGF-C and VEGF-D are contributing via VEGFR3 signaling to the process of lumen obliteration and perivascular inflammation.…”

Section: Discussionmentioning

confidence: 89%

Vascular Endothelial Growth Factor Receptor 3 Signaling Contributes to Angioobliterative Pulmonary Hypertension

et al. 2015

View full text Add to dashboard Cite

The mechanisms involved in the development of severe angioobliterative pulmonary arterial hypertension (PAH) are multicellular and complex. Many of the features of human severe PAH, including angioobliteration, lung perivascular inflammation, and right heart failure, are reproduced in the Sugen 5416/ chronic hypoxia (SuHx) rat model. Here we address, at first glance, the confusing and paradoxical aspect of the model, namely, that treatment of rats with the antiangiogenic vascular endothelial growth factor (VEGF) receptor 1 and 2 kinase inhibitor, Sugen 5416, when combined with chronic hypoxia, causes angioproliferative pulmonary vascular disease. We postulated that signaling through the unblocked VEGF receptor VEGFR3 (or flt4) could account for some of the pulmonary arteriolar lumen-occluding cell growth. We also considered that Sugen 5416-induced VEGFR1 and VEGFR2 blockade could alter the expression pattern of VEGF isoform proteins. Indeed, in the lungs of SuHx rats we found increased expression of the ligand proteins VEGF-C and VEGF-D as well as enhanced expression of the VEGFR3 protein. In contrast, in the failing right ventricle of SuHx rats there was a profound decrease in the expression of VEGF-B and VEGF-D in addition to the previously described reduction in VEGF-A expression. MAZ51, an inhibitor of VEGFR3 phosphorylation and VEGFR3 signaling, largely prevented the development of angioobliteration in the SuHx model; however, obliterated vessels did not reopen when animals with established PAH were treated with the VEGFR3 inhibitor. Part of the mechanism of vasoobliteration in the SuHx model occurs via VEGFR3. VEGFR1/VEGFR2 inhibition can be initially antiangiogenic by inducing lung vessel endothelial cell apoptosis; however, it can be subsequently angiogenic via VEGF-C and VEGF-D signaling through VEGFR3.

show abstract

Section: Discussionmentioning

confidence: 89%

Vascular Endothelial Growth Factor Receptor 3 Signaling Contributes to Angioobliterative Pulmonary Hypertension

et al. 2015

View full text Add to dashboard Cite

show abstract

“…In contrast, Ozaki described it as TSC403 with the specific expression in the lungs and overexpression in breast cancer cells. Significant similarity to the other LAMP family proteins-LAMP1 and LAMP2, was observed [1].…”

Section: Introductionmentioning

confidence: 93%

“…LAMP proteins are highly glycosylated type 1 lysosomaltransmembrane glycoproteins [1] [2]. They are located mainly in the lysosomal membrane [3] and are rarely found on the surface of normal cells, most commonly occurring in cancer cells [1] [4].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Transcriptional Activity of LAMP3 Gene Involved in Autophagocytosis in Colorectal Cancer LAMP3 Expression in Colorectal Cancer

Bednarczyk¹,

Muc-Wierzgoń²,

Zmarzły³

et al. 2017

JBM

View full text Add to dashboard Cite

Background: Autophagocytosis is a biological process involving the controlled distribution of cell fragments and organelles in order to obtain an additional source of energy. LAMP3 (lysosome-associated membrane protein 3) is a heavily glycosylated integral membrane protein located mainly in the lysosomal membrane. Recent studies have shown that it participates in tumor metastasis and drug resistance. Its main role is contribution to tumor cells proliferation, migration and invasion. The aim of this study was to determine changes in transcriptional activity of LAMP3 at various stages of colorectal cancer. In addition, an attempt was made to select miRNAs potentially regulating LAMP3 expression using bioinformatic databases. Methods: The study was conducted on healthy colon samples and colon cancer samples in four stages. Molecular analysis included the extraction of total RNA, purification of the obtained extracts, expression profile analysis using oligonucleotide microarray technique and in silico determination of miRNAs potentially regulating the LAMP3 expression. Results: The level of LAMP3 expression is higher in colorectal adenocarcinoma cells than in non-cancerous cells and depends on the stage of the disease. Conclusions: LAMP3 may promote cancer progression, metastasis and cause the resistance to treatment.

show abstract

“…Some researches suggest that PERK/elfa has involved in hypoxia resistance and tumor growth. Nagelkerke et al 12 found in breast cancer that LAMP3 protein expression was established to be of prognostic relevance and was related with locoregional recurrence, tumor grade, size, lymph node, resistance to therapy, and steroid hormone receptor status. What's more, previous information suggested that LAMP3 expression was related with resistance to chemotherapy and radiotherapy.…”

Section: Introductionmentioning

confidence: 99%

LAMP3 expression correlated with poor clinical outcome in human ovarian cancer

et al. 2017

View full text Add to dashboard Cite

Lysosome-associated membrane protein 3 belongs to the lysosome-associated membrane glycoprotein family, which is associated with lymph node, metastasis, poor overall survival, and resistance to chemotherapy and radiotherapy. Epithelial ovarian cancer is one of the most deadly global female gynecologic malignant tumors. Its clinical outcome is poor and most epithelial ovarian cancer patients tend to relapse because of drug resistance. However, lysosomeassociated membrane protein 3 expression in epithelial ovarian cancer and its relationship between clinicopathologic factors remain poorly understood. To clarify the prognostic implications of lysosome-associated membrane protein 3 in epithelial ovarian cancer, we analyzed both messenger RNA and protein levels of lysosome-associated membrane protein 3 in ovarian carcinomas. Polymerase chain reaction results showed higher expression of lysosome-associated membrane protein 3 messenger RNA in epithelial ovarian cancer than in noncancerous tissues. Immunohistochemical results showed that high lysosome-associated membrane protein 3 cytoplasmic expression was significantly related to tumor grade (p = 0.038), lymph node metastasis (p = 0.049), metastasis (p < 0.001), level of CA125 (p = 0.030), and International Federation of Gynecology and Obstetrics (FIGO) (p < 0.001). High lysosome-associated membrane protein 3 nuclear expression was significantly associated with tumor grade (p = 0.046), tumor single or double (representative whether the tumor involving one or both ovaries) (p = 0.016), metastasis (p < 0.001), and FIGO stage (p < 0.001). Survival analysis indicated that high lysosome-associated membrane protein 3 cytoplasmic expression (hazard ratio: 4.632, 95% confidence interval: 2.421-8.864; p < 0.001), patients' age (hazard ratio: 1.729, 95% confidence interval: 1.027-2.911; p = 0.039), and FIGO stage (hazard ratio: 2.049, 95% confidence interval: 1.113-3.774; p = 0.021) were significantly correlated with poor survival outcome of epithelial ovarian cancer patients.

show abstract

Hypoxic regulation and prognostic value of LAMP3 expression in breast cancer

Cited by 61 publications

References 32 publications

Vascular Endothelial Growth Factor Receptor 3 Signaling Contributes to Angioobliterative Pulmonary Hypertension

Vascular Endothelial Growth Factor Receptor 3 Signaling Contributes to Angioobliterative Pulmonary Hypertension

The Transcriptional Activity of LAMP3 Gene Involved in Autophagocytosis in Colorectal Cancer LAMP3 Expression in Colorectal Cancer

LAMP3 expression correlated with poor clinical outcome in human ovarian cancer

Contact Info

Product

Resources

About