LAMP3

Official Full Name

lysosomal associated membrane protein 3

Organism

Homo sapiens

GeneID

27074

Background

Dendritic cells (DCs) are the most potent antigen-presenting cells. Immature DCs efficiently capture antigens and differentiate into interdigitating dendritic cells (IDCs) in lymphoid tissues that induce primary T-cell responses (summary by de Saint-Vis et al., 1998 [PubMed 9768752]).[supplied by OMIM, Dec 2010]

Synonyms

LAMP; CD208; DCLAMP; LAMP-3; TSC403; DC LAMP; DC-LAMP;

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Detailed Information

Recent Progress

Lysosomal associated membrane protein 3 (LAMP3) is a tumor-specific and hypoxia-induced protein. It is a downstream target gene of tumor suppressor TP53 and its expression has been associated with hypoxia-induced metastasis and poor overall survival in cervical, breast and gastrointestinal cancers. It may also serve as a molecular marker of mature dendritic cells. Its expression was induced by hypoxia, and was associated with hypoxia mediated metastasis in breast and cervical cancers.

To determine LAMP3 protein expression in laryngeal squamous cell carcinoma (LSCC) and its prognostic value, researchers identified protein expression of LAMP3 and TP53 in LSCC tissues, which was correlated with patients' clinical parameters and overall survival. LAMP3 and TP53 protein expression was significantly higher in cancerous tissues compared to adjacent normal surgical margin tissues. Both high LAMP3 and high TP53 protein expression were significantly associated with tumor stage and size. Significant correlation between LAMP3 and TP53 expression was observed. Patients with high LAMP3 or high TP53 expression had a poor overall survival. These findings suggest that both epithelial LAMP3 expression and TP53 expression are independent prognostic markers for LSCC.

In another research, investigators determined protein expression of LAMP3 and TP53 in both gastric and colorectal tissues. It was revealed that LAMP3 and TP53 protein expression was significantly higher in cancerous tissues compared to normal and benign tissues. In both gastric and colorectal cancers, high LAMP3 protein expression was significantly associated with tumor stage. However no correlation between LAMP3 and TP53 expression was observed. Patients with high LAMP3 expression but not high TP53 expression had a poor overall survival. These findings suggest that epithelial LAMP3 expression is an independent prognostic marker for gastrointestinal cancer.

To elucidate the epithelial expression of LAMP3 and its prognostic value in esophageal squamous cell carcinoma (ESCC), mRNA expression of LAMP3 in 157 ESCC tissues and 50 adjacent normal tissues was detected by qRT-PCR. The results showed that both mRNA and protein expression level of LAMP3 were significantly higher in cancerous tissues compared with normal controls. LAMP3 DNA copy number was amplified in 70% of ESCC tissues and positive correlated with mRNA expression. Furthermore, patients with higher LAMP3 expression had worse overall survival and disease-free survival. In conclusion, these results suggest that epithelial LAMP3 expression is an independent prognostic biomarker for ESCC.

In order to examine the hypoxic regulation of the PKR-like endoplasmic reticulum kinase (PERK)/activating transcription factor-4 (ATF4)/LAMP3-arm of the unfolded protein response (UPR) in head and neck squamous cell carcinoma (HNSCC), LAMP3 expression was determined in patient biopsies. It was found that mRNA and protein expression for PERK, ATF4, and LAMP3 was evaluated after hypoxic exposure of HNSCC cell lines. Moreover, in patients with HNSCC, high LAMP3 expression and the occurrence of distant metastases during follow-up was discovered. Patients with high LAMP3 levels had a worse metastasis-free survival. Exposure to endoplasmic reticulum-stress stimulated PERK, ATF4, and LAMP3 expression. In conclusion, LAMP3 is relevant for prognosis in HNSCC. However, the PERK/ATF4/LAMP3-arm of the UPR responded differently to hypoxia in HNSCC compared to other tumor types.

References:

Qiu, X., You, Y., Huang, J., Wang, X., Zhu, H., & Wang, Z. (2015). Lamp3 and tp53 overexpression predicts poor outcome in laryngeal squamous cell carcinoma. International Journal of Clinical & Experimental Pathology, 8(5), 5519.
Sun, R., Wang, X., Zhu, H., Mei, H., Wang, W., & Zhang, S., et al. (2014). Prognostic value of lamp3 and tp53 overexpression in benign and malignant gastrointestinal tissues. Oncotarget, 5(23), 12398-12409.
Wang, Y. Q., Tang, B. S., Yu, R. L., Li, K., Liu, Z. H., & Xu, Q., et al. (2014). Association analysis of stk39, mccc1/lamp3 and sporadic pd in the chinese han population. Neuroscience Letters, 566(18), 206-209.
Liao, X., Chen, Y., Liu, D., Li, F., Li, X., & Jia, W. (2015). High expression of lamp3 is a novel biomarker of poor prognosis in patients with esophageal squamous cell carcinoma. International Journal of Molecular Sciences, 16(8), 17655-17667.
Nagelkerke, A., Sweep, F. C., Stegeman, H., Grénman, R., Kaanders, J. H., & Bussink, J., et al. (2015). Hypoxic regulation of the perk/atf4/lamp3-arm of the unfolded protein response in head and neck squamous cell carcinoma. Head & Neck, 37(6), 896-905.

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