Chromatin streaming from giant polyploid nuclei in Ishikawa endometrial hollow spheroids results in the amitotic proliferation of nuclei that fill the spheroid envelope
- Published
- Accepted
- Subject Areas
- Cell Biology, Histology
- Keywords
- Chromatin streaming, hollow spheroids, amitotic proliferation, Cell dogma, Gas vacuoles, Colonies of nuclei, mitonucleons
- Copyright
- © 2019 Fleming
- Licence
- This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ Preprints) and either DOI or URL of the article must be cited.
- Cite this article
- 2019. Chromatin streaming from giant polyploid nuclei in Ishikawa endometrial hollow spheroids results in the amitotic proliferation of nuclei that fill the spheroid envelope. PeerJ Preprints 7:e27463v1 https://doi.org/10.7287/peerj.preprints.27463v1
Abstract
This paper describes the amitotic proliferation of nuclei that fill the envelope of Ishikawa hollow spheroids. The presence of hollow spheroids in malignant ascites fluid has intrigued cancer researchers, but little is understood about how they form. Observations in Ishikawa endometrial cell cultures demonstrate that nuclei filling the spheroid envelope are generated amitotically by the same mechanism responsible for cell formation in domes. Transient structures of aggregated chromatin surrounded by fused giant mitochondria, the initiating structure for dome formation, are also the starting point for the differentiation of unicellular polyploid hollow spheroids. Nuclei from monolayer cells are aggregated in a single enlarged cell where they become surrounding by giant fused mitochondria. A gaseous vacuole forms inside the mitonucleon extending it so that all of the cell material, including nuclei is pressed against the cell membrane. The resulting unicellular hollow spheroid detaches from the colony, capable of migration from the site of its formation. Ultimately, pressure on the aggregated chromatin results in the release of streams of chromatin granules that initially travel as if guided by microtubules through the shell of the hollow spheroid. Granules dissolve into filaments and, as initially described in dome formation, this material self-assembles into clusters of nuclei. Nuclei move out of these clusters into a regular array within the spheroid envelope, with formation of cell membranes as the final step in the creation of multicellular hollow spheroids. The curved membrane characteristic of domes and spheroids, as well as colonies of nuclei produced by amitosis have been identified in tumor tissue that survives chemotherapy, suggesting that amitotic cell proliferation may at least partially explain the population of cancer tumor cells in humans that are resistant to chemotherapy.
Author Comment
Investigations begun in 1994 were designed to describe the process of differentiation of domes in cultured human endometrial cells. Almost every discovery along the way moved me into fascinating and unexpected realms such as the variety of mitochondrial morphology and function that I needed to master in order to make sense of a transient structure made up of aggregated chromatin and fused mitochondria essential to the differentiation process. But probably no result was more unexpected than observations suggesting that epithelial dome cells, that can extend out into gland-like structures, arise amitotically (any proliferation process that is not mitosis. As I learned, there are various kinds of amitosis. The amitotic process I have observed has not been described before, and I have called it amitosis by chromatin streaming. I described its occurrence in differentiation of domes and have since discovered that chromatin streaming is responsible for the formation of multicellular hollow spheroids, at least in human endometrial epithelia, as described in this paper. Hollow spheroids are of great interest to scientists researching cancer biology since they have been implicated in metastases. Furthermore, evidence from the laboratories of a few of the scientists researching cancer, particularly cancer that escapes chemotherapeutic measures, suggests that amitosis by chromatin streaming can contribute to human tumor cell mass. Suddenly what started out as research into differentiation, a mostly unexplored process, has resulted in studies that may be of use to biologists and physicians working in the trenches against "The Emperor of All Maladies," a well explored pheomenon that still holds some secrets. That is the beauty of pure research.