J Cancer 2018; 9(24):4726-4735. doi:10.7150/jca.26502

Review

Spontaneous Cancers, But Not Many Induced Ones in Animals, Resemble Semi-New Organisms that Possess a Unique Programmed Cell Death Mode Different from Apoptosis, Senescent Death, Necrosis and Stress-Induced Cell Death

Mingjun Shi1✉, Haiyan Zhou2, Mingjuan Lei3, Lichan Chen3, Lucas Zellmer4, Yan He5, Wenxiu Yang6, Ningzhi Xu7✉, Dezhong Joshua Liao5,6✉

1. Department of Pathophysiology, Guizhou Medical University, Guiyang 550025, Guizhou Province, China.
2. Clinical Research Center, Guizhou Medical University Hospital, Guiyang 550004, Guizhou Province, China
3. Hormel Institute, University of Minnesota, Austin, MN 55912, USA
4. Masonic Cancer Center, University of Minnesota, 435 E. River Road, Minneapolis, MN 55455, USA
5. Key Lab of Endemic and Ethnic Diseases of the Ministry of Education of China at Guizhou Medical University, Guiyang 550004, Guizhou Province, China
6. Department of Pathology, Guizhou Medical University Hospital, Guiyang 550004, Guizhou province, China
7. Laboratory of Cell and Molecular Biology & State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China

Abstract

There are four basic cell death modes in animals, i.e. physiological senescent death (SD) and apoptosis as well as pathological necrosis and stress-induced cell death (SICD). There have been numerous publications describing “apoptosis” in cancer, mostly focused on killing cancer cells using radio- or chemo-therapy, with few on exploring how cancer cells die naturally without such treatments. Spontaneous benign or malignant neoplasms are immortal and autonomous, but they still retain some allegiance to their parental tissue or organ and thus are still somewhat controlled by the patient's body. Because of these properties of immortality, semi-autonomy, and semi-allegiance to the patient's body, spontaneous tumors have no redundant cells and resemble “semi-new organisms” parasitizing the patients, becoming a unique tissue type possessing a hitherto unannotated cell death mode besides SD, apoptosis, necrosis and SICD. Particularly, apoptosis aims to expunge redundant cells, whereas this new mode does not. In contrast to spontaneous tumors, many histologically malignant tumors induced in experimental animals, before they reach an advanced stage, regress after withdrawal of the inducer. This mortal and non-autonomous nature disqualifies these animal lesions as authentic neoplasms and as semi-new organisms but makes them a good tissue type for apoptosis studies. Ruminating over cell death in spontaneous cancers and many inauthentic tumors induced in animals from these new slants makes us realize that “whether cancer cells undergo apoptosis” is not an easy question with a simple answer. Our answer is that cancer cells have an uncharacterized programmed cell death mode, which is not apoptosis.

Keywords: apoptosis, programmed cell death, necrosis, cancer, tumor, in vivo, senescence

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How to cite this article:
Shi M, Zhou H, Lei M, Chen L, Zellmer L, He Y, Yang W, Xu N, Liao DJ. Spontaneous Cancers, But Not Many Induced Ones in Animals, Resemble Semi-New Organisms that Possess a Unique Programmed Cell Death Mode Different from Apoptosis, Senescent Death, Necrosis and Stress-Induced Cell Death. J Cancer 2018; 9(24):4726-4735. doi:10.7150/jca.26502. Available from http://www.jcancer.org/v09p4726.htm