Tumor can originate from not only rare cancer stem cells

TL;DR

This study combines mathematical modeling and experimental data to show that tumors can originate from non-cancer stem cells, challenging the traditional view that only rare CSCs are tumor-initiating.

Contribution

It provides evidence that the number of tumorigenic cells exceeds the number of CSCs and that non-CSCs can also initiate tumors, supported by both theoretical and experimental approaches.

Findings

Non-CSCs can initiate tumors if proliferation potential is sufficient.

A significant proportion of tumor cells are potentially tumorigenic in murine models.

Tumors may originate from a broader cell population than just rare CSCs.

Abstract

Tumors are believed to consist of a heterogeneous population of tumor cells originating from rare cancer stem cells (CSCs). However, emerging evidences show that tumor may also originate from non-CSCs. Here, we give evidences supporting that the number of tumorigenic tumor cells is higher than the number of CSCs and tumor can also derive from non-CSCs. First, we applied an idealized mathematical model and theoretically calculated that non-CSCs could initiate tumor if their proliferation potential was adequate. Next, we demonstrated by experimental studies that 17.7%, 38.6% and 5.2% of tumor cells in murine B16 solid melanoma, H22 hepatoma and Lewis lung carcinoma, respectively, were potentially tumorigenic. We propose that the rare CSCs, if exist, are not the only origination of a tumor.