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The Migration Ability of Stem Cells Can Explain the Existence of Cancer of Unknown Primary Site. Rethinking Metastasis

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The Migration Ability of Stem Cells Can Explain the Existence of Cancer of Unknown Primary Site. Rethinking Metastasis

Miguel López-Lázaro. Oncoscience.

Abstract

Cancers of unknown primary site are metastatic cancers for which primary tumors are not found after detailed investigations. In many cases, the site of origin is not identified even on postmortem examination. These cancers are the fourth most common cause of cancer death. The biological events involved in the development of this type of cancers remain unknown. This manuscript discusses that, like metastatic cells, stem cells have a natural ability to migrate. A cancer of unknown primary site would form when deregulated, premalignant or cancerous stem cells migrated away from their natural tissue and gave rise to a cancer in a new site before or without generating a tumor in their original tissue. It is important to realize that forming a tumor in a tissue is not a prerequisite for stem cells to migrate away from that tissue. This view is in accordance with recent observations that strongly support the tumorigenesis model in which cancer arises from normal stem cells. Evidence has accumulated that cancer stem cells may play a key role in cancer progression and resistance to therapy. Successful treatment of cancer, including that of unknown primary site, may therefore require the development of therapies against cancer stem cells.

Keywords: Cancer of unknown origin; Cancer stem cells; Cancer therapy; Cells of origin in cancer; Stem cell model of cancer.

Conflict of interest statement

CONFLICT OF INTEREST

The author declares no conflict of interest.

Figures

Figure 1
Figure 1. The migration ability of stem cells can explain the existence of cancer of unknown primary site
A cancer of unknown primary site would form when deregulated stem cells, premalignant stem cells or cancer stem cells migrated away from their natural tissue (primary site) and formed a tumor in another tissue (secondary site) before or without generating a tumor in their primary location. Thick arrows represent the probably most common pathway for metastasis. Curved arrows represent self-renewal capacity. See text for further details.
Figure 2
Figure 2. The stem cell model of cancer can explain the age distribution of cancer
A) Age is the most important cancer risk factor, and cancer incidence increases with age. B) Stem cells self-renew, have a long lifespan, and are the only cells that transmit the DNA of the zygote to the cells we have at the time of death. Stem cells can differentiate into progenitor cells and eventually into differentiated cells. C) Stem cells can acquire and accumulate DNA alterations during our whole life. Because progenitor cells lack an innate ability to self-renew and have a relatively short lifespan (until they fully differentiate), they can acquire and accumulate DNA alterations only during relatively short periods of our life. The model in which cancer arises from stem cells fits the age distribution of cancer better than the model in which cancer initiates in progenitor cells. Curved arrows represent self-renewal capacity. SC: stem cell; PC: progenitor cell; DC: differentiated cell.

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