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. 2006 Aug 28;103(36):13474–13479. doi: 10.1073/pnas.0606053103

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© 2006 by The National Academy of Sciences of the USA

Freely available online through the PNAS open access option.

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Fig. 1. — Tumor progression can reach full malignancy before any one cell accumulates each of the necessary mutations. (a) Traditional view of tumor progression: Competition. Genetically unstable partially transformed cells (●) proliferate. The cells compete for limited oxygen, essential nutrients, and GFs; therefore, many die (). Eventually, one cell accumulates sufficient mutations to express all of the functions required for a clone of fully malignant cells to emerge (●). (b) Hypothesis of tumor progression: Cooperation. Genetically unstable partially transformed cells (●) proliferate and yield different mutant cell types (, ). The different cell types cooperate with each other, enabling them to survive and proliferate. The concept of cooperation among partially transformed cells is added to the traditional view of tumor progression. As in the traditional view, eventually one cell may accumulate sufficient mutations to express all of the functions required for a clone of fully malignant cells to emerge (●). An example of cells that cooperate by producing different GFs is shown in Fig. 2.

Inline graphic — Tumor progression can reach full malignancy before any one cell accumulates each of the necessary mutations. (a) Traditional view of tumor progression: Competition. Genetically unstable partially transformed cells (●) proliferate. The cells compete for limited oxygen, essential nutrients, and GFs; therefore, many die (). Eventually, one cell accumulates sufficient mutations to express all of the functions required for a clone of fully malignant cells to emerge (●). (b) Hypothesis of tumor progression: Cooperation. Genetically unstable partially transformed cells (●) proliferate and yield different mutant cell types (, ). The different cell types cooperate with each other, enabling them to survive and proliferate. The concept of cooperation among partially transformed cells is added to the traditional view of tumor progression. As in the traditional view, eventually one cell may accumulate sufficient mutations to express all of the functions required for a clone of fully malignant cells to emerge (●). An example of cells that cooperate by producing different GFs is shown in Fig. 2.