Identification of Metastatic Cell Nucleus in Human Prostate Cancer by Electron Microscopy

Abstract

Aim: Metastatic prostate cancer is responsible for a large proportion of deaths worldwide. The aim of this study was to identify metastatic cells and determine if stromal invasion by cancer cells differs from those during metastasis. Methods & results: Tissue biopsy/prostatectomy samples, visualized by transmission electron microscopy, identified that metastatic cells are a lineage of stem cells, which have dedifferentiated into cancerous columnar/cuboidal cells. These cells demonstrate nuclear plasticity; the loss of nuclear membranes and boundary between nucleus and cytoplasm; and the presence of electron dense molecules, which can readily pass through basement membranes and enter the capillary, ready for dissemination to metastatic sites. Conclusion: This is the first study to demonstrate differences between invasive and metastatic cell types.

Lay abstract

Being able to identify metastatic prostate cancer at the initial point of diagnosis could result in earlier targeted treatment, which could extend the patients life. Here, we identified that the source of metastasis is dedifferentiated columnar/cuboidal cells, visualized through transmission electron microscopy. Additionally, these have morphologically distinct characteristics from invasive cancer cells. These include nuclear plasticity; the loss of nuclear membranes and boundary between nucleus and cytoplasm; and the presence of electron dense molecules. This is the first study to demonstrate differences between invasive and metastatic cell types.

Keywords:

• cancer requires mutation
• chromatin harbors mutated DNA/genes
• electron dense DNA molecules
• invasive and metastatic cell types
• loss of nuclear membranes releases DNA/genes
• mutation imparts proliferation advantage
• nuclear plasticity is indicative of the metastatic cell

Acknowledgments

This research was supported in part by the Research Service of the Minneapolis Veterans Affairs Medical Center by providing laboratory and other research facilities to AA Sinha. The author works as a WOC (work without compensation) or any salary from the VA and a token salary from the University not involving the State or Federal funds. The author is grateful to DF Gleason and NA Staley for grading prostate cancer sections, former pathologists of the Minneapolis VA Medical Center. The author is also grateful to CE Blackard and his associates for biopsy and prostatectomy specimens. The author thanks FE Pomroy, Jr. formerly of the Minneapolis VA Medical Center for making sections for this study. The author is grateful to JS Hungaski, Jr. and J Erickson of the VAMC Media Service for making the final figures, and to the staff of the Departments of Surgical Pathology, Library, and the Research Service, Minneapolis VA Medical Center. The author thanks MK Grace and D Sinha for helpful comments and critical proof reading of the manuscript. The author is grateful to Miss Lauren Woolfe, Assistant Editor, who has helped the author to navigate through the submission and editorial process. The author is also grateful to the reviewers who helped in the revision of this manuscript.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The author states that he has obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.