1. a.
Good prognosis
Poor prognosis
Metastasis b.
Good prognosis
Metastatic variants
Metastasis c.
Metastasis
Good prognosis
Poor prognosis

2. a.
Separate
origins
Normal tissue
Poor prognosis b.
Clonal progression
BUT - are the tumors homogeneous even for primary tumor growth

3. CD44+ / B38.1+
CD24lo
Lin-

4. Lin- / CD44+ / CD24lo
Cells are tumorigenic
They comprise minority of
cells in tumor
They don’t have a growth
advantage

5. Lin- / CD44+ / CD24lo cells are tumorigenic
Sorting for ESA+ further enriches - only a few % of cells in tumor.

6. T1
200 P1
sorted P2 T2
1000
Lin- / CD44+ / CD24lo cells regenerate the mixture of cell types
thru 4 passages

7. Therefore tumors contain rare, self-renewing cells that
are tumorigenic and can regenerate multiple cell types
That is, tumor stem cells or tumor-initiating cells.
Most cells in the tumor lack these properties.
Therapy should be directed at the subset, not the majority.

8. Micrometastases
Present in 30% of BrCa patients but only 50% eventually
progress to clinically evident tumors within 5 years
Are they a mix of rare malignant seeds and other
non-malignant seeds?
Or do they reflect seeding of a homogeneous set of
premalignant cells with a uniform
probability of forming frank tumors?

11. Good prognosis
Stromal
response
Metastatic
variants
Poor prognosis
Metastasis