A pilot study on morphology and the mechanism involved in linearly patterned programmed cell necrosis in melanoma

Han,Chunrong; Sun,Baocun; Wang,Wei; Cai,Wenjuan; Lou,Dan; Sun,Yan; Zhao,Xiulan

doi:10.3892/ol_00000144

A pilot study on morphology and the mechanism involved in linearly patterned programmed cell necrosis in melanoma

Authors:
- Chunrong Han
- Baocun Sun
- Wei Wang
- Wenjuan Cai
- Dan Lou
- Yan Sun
- Xiulan Zhao
View Affiliations

Affiliations: Department of Pathology, Tianjin Cancer Hospital and Institute, Tianjin Medical University, Tianjin, P.R. China
Published online on: September 1, 2010 https://doi.org/10.3892/ol_00000144
Pages: 821-826

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Accumulating data provide evidence that autophagy contributes to programmed cell death (PCD) under certain circumstances. Immunohistochemistry and real-time PCR were performed to investigate the correlation the expression of autophagy-related proteins LC3 and Atg4B and linearly patterned programmed cell necrosis (LPPCN) in melanoma. LPPCN was recently reported to be a special PCD, which is similar to neither apoptosis nor conventional necrosis commonly observed in tumoral tissues. The mechanism involved in LPPCN remains unclear. Our data showed that the expression of LC3 and Atg4B in the LPPCN-positive group was significantly higher than that in the LPPCN-negative group regarding protein and mRNA levels (p<0.05). Based on morphological observation, immunohistochemistry and real-time PCR experiments in this study, it was concluded that autophagy may play a crucial role in the process of LPP+CN in melanoma. This study provides novel insights into the mechanism that regulates LPPCN in vivo during tumor development. We speculated that LPPCN may be an early stage event in tumoral neovascularization under hypoxic-microenvironmental conditions. Accordingly, LPPCN can be considered a novel target in the process of antiangiogenesis treatment, which can be expected to obtain a better clinical outcome in the future.

View Figures

View References

1	McKinnon JG, Yu XQ, McCarthy WH, et al: Prognosis for patients with thin cutaneous melanoma: long-term survival data from New South Wales Central Cancer Registry and the Sydney Melanoma Unit. Cancer. 98:1223–1231. 2003. View Article : Google Scholar : PubMed/NCBI
2	American Cancer Society. Cancer Facts And Figures. GA: American Cancer Society; Atlanta: 2008
3	Zhang SW, Li M, Zhang DF, et al: Hypoxia influences linearly patterned programed cell necrosis and tumor blood supply patterns formation in melanoma. Lab Invest. 89:575–586. 2009. View Article : Google Scholar : PubMed/NCBI
4	Assuncao Guimaraes C and Linden R: Programmed cell deaths. Apoptosis and alternative deathstyles. Eur J Biochem. 271:1638–1650. 2004.PubMed/NCBI
5	Zong WX and Thompson CB: Necrotic death as a cell fate. Genes Dev. 20:1–15. 2006. View Article : Google Scholar : PubMed/NCBI
6	Yuan J, Lipinski M and Degterev A: Diversity in the mechanisms of neuronal cell death. Neuron. 40:401–413. 2003. View Article : Google Scholar : PubMed/NCBI
7	Zong WX, Ditsworth D, Bauer DE, et al: Alkylating DNA damage stimulates a regulated form of necrotic cell death. Genes Dev. 18:1272–1282. 2004. View Article : Google Scholar : PubMed/NCBI
8	Edinger AL and Thompson CB: Death by design: apoptosis, necrosis and autophagy. Curr Opin Cell Biol. 16:663–669. 2004. View Article : Google Scholar : PubMed/NCBI
9	Kitanaka C and Kuchino Y: Caspase-independent programmed cell death with necrotic morphology. Cell Death Differ. 6:508–515. 1999. View Article : Google Scholar : PubMed/NCBI
10	Satoo K, Noda NN, Kumeta H, et al: The structure of Atg4B-LC3 complex reveals the mechanism of LC3 processing and delipidation during autophagy. EMBO J. 28:1341–1350. 2009. View Article : Google Scholar : PubMed/NCBI
11	Philip EL, Burg G, David W and Sarasain A: World Health Organization Classification of Tumours Pathology and Genetics of Skin Tumours. IARC Press; Lyon: 2006
12	Bursch W, Ellinger A, Gerner C, Fröhwein U and Schulte-Hermann R: Programmed cell death (PCD). Apoptosis, autophagic PCD, or others? Ann NY Acad Sci. 926:1–12. 2000. View Article : Google Scholar : PubMed/NCBI
13	Tolkovsky AM: Mitochondrial disappearance from cells: a clue to the role of autophagy in programmed cell death and disease? Biochimie. 84:233–240. 2002. View Article : Google Scholar : PubMed/NCBI
14	Larsen KE and Sulzer D: Autophagy in neurons: a review. Histol Histopathol. 17:897–908. 2002.PubMed/NCBI
15	Cuervo AM: Autophagy: in sickness and in health. Trends Cell Biol. 14:70–77. 2004. View Article : Google Scholar : PubMed/NCBI
16	Osterlind A: Epidemiology on malignant melanoma in Europe. Acta Oncol. 31:903–908. 1992. View Article : Google Scholar : PubMed/NCBI
17	Karim-Kos HE, de Vries E, Soerjomataram I, Lemmens V, Siesling S and Coebergh JW: Recent trends of cancer in Europe: a combined approach of incidence, survival and mortality for 17 cancer sites since the 1990s. Eur J Cancer. 44:1345–1389. 2008. View Article : Google Scholar : PubMed/NCBI
18	Yakolev AG and Faden AI: Mechanisms of neural cell death: implications for development of neuroprotective treatment strategies. NeuroRx. 1:5–16. 2004. View Article : Google Scholar : PubMed/NCBI
19	Proskuryakov SY, Gabai VL and Konoplyannikov AG: Necrosis is an active and controlled form of programmed cell death. Biochemistry (Mosc). 67:387–408. 2002. View Article : Google Scholar : PubMed/NCBI
20	Lugovskoy AA, Degterev AI, Fahmy AF, et al: A novel approach for characterizing protein ligand complexes: molecular basis for specificity of small-molecule Bcl-2 inhibitors. J Am Chem Soc. 124:1234–1240. 2002. View Article : Google Scholar : PubMed/NCBI
21	Wyllie AH, Kerr JF and Currie AR: Cell death: the significance of apoptosis. Int Rev Cytol. 68:251–306. 1980. View Article : Google Scholar
22	Jia YL, Li J, Qin ZH and Liang ZQ: Autophagic and apoptotic mechanisms of curcumin-induced death in K562 cells. J Asian Nat Prod Res. 11:918–928. 2009. View Article : Google Scholar : PubMed/NCBI
23	Folkman J: Tumor angiogenesis: therapeutic implications. N Engl J Med. 285:1182–1186. 1971. View Article : Google Scholar : PubMed/NCBI
24	Carmeliet P: Mechanisms of angiogenesis and arteriogenesis. Nat Med. 6:389–395. 2000. View Article : Google Scholar : PubMed/NCBI
25	Tannock IF and Hayashi S: The proliferation of capillary endothelial cells. Cancer Res. 32:77–82. 1972.PubMed/NCBI
26	Folkman J and Hochberg M: Self-regulation of growth in dimensions. J Exp Med. 138:745–753. 1973. View Article : Google Scholar : PubMed/NCBI