stem cells and cancer

2. Table of contents
• Introduction
• History of origin of cancer
• The stem cell theory of cancer
• Similarities between SC’s and CSC’s
• Do CSCs Arise From Stem Cells?
• Examples
• Conclusion
• References

4. WHAT ARE STEM
CELLS?
“Cells that can reproduce themselves
and give rise to other kinds of
cells”

5. WHAT IS CANCER?
• The term "cancer" describes a group of
diseases that are characterized by
uncontrolled cellular growth, cellular
invasion into adjacent tissues, and the
potential to metastasize if not treated at a
sufficiently early stage.
BENIGN
MALIGNANT

8. History of origin of
cancer
• Although cancer researchers first isolated CSCs in
1994, the concept dates to the mid-19th century.
• 1855- German pathologist Rudolf Virchow
proposed that cancers arise from the activation of
dormant, embryonic-like cells present in mature
tissue.
• 1874 – Durante - hypothesis of cancer origin from
a rare population of normal cells with stem cell
properties
• 1875 – Cohnheim - embryonal rest theory--
tumors develop from embryonic rests that do not p
articipate in the formation of normal surrounding

9. Continued…..
• 1956 – Makino - Further evidence favoring
the concept of the stem cell in ascites
tumors of rats
• 1963 - Bruce & Van Der Gaag - A
quantitative assay for the number of
murine lymphoma cells capable of
proliferation in vivo.
• 1977 - Hamburger and Salmon -
hypothesis that some cancers contain a
small subpopulation of cells that are
similar to normal stem cells

10. Continued….
• 1994--Lapidot and colleagues provided the
first solid evidence, they used cell-surface
protein markers to identify a relatively rare
population of stem like cells in acute myeloid
leukemia
• 1997--Cancer stem cells were first identified
by JOHN DICK in acute myeloid leukemia
• In 2003, Michael Clarke of the University of
Michigan and now at Stanford, found cancer
stem cells in breast tumors and demonstrated
that most other cells in the tumor were
incapable of seeding growth on their own.

11. The stem cell theory of
cancer
• The stem cell theory of cancer
PROPOSES that
“Among all cancerous cells, a few act as
stem cells that reproduce themselves and
sustain the cancer, much like normal stem
cells normally renew and sustain our
organs and tissues.”

12. Cancer stem cells
• In 2006 consensus panel convened by the
American Association of Cancer Research
has defined a CSC as
“A cell within a tumor that possesses the
capacity to self-renew and to cause the
heterogeneous lineages of cancer cells that
comprise the tumor”
this definition does not indicate the source of
these cells like from stem, progenitor, or
differentiated cells….
• tumor-initiating cell" or "cancer-initiating cell

14. The stem cell theory of
cancer
• Implications:
1- Tumor can regrow…
An analogy would be a weeding technique
that is evaluated based on how low it can
chop the weed stalks—but no matter how
low the weeks are cut, if the roots aren’t
taken out, the weeds will just grow back.

17. Continued…..
2- Cancer stem cells that give rise to
metastasis
3- Cancer stem cells are closely related to
normal stem cells and will share many of the
behaviors and features of those normal stem
cells.
The Theory, therefore, is that
“cancer stem cells arise out of normal stem
cells

18. Similarities between SCs and
CSCs
 Long life span
 Relative apoptosis resistance
 Asymmetric division
 Relative slow proliferation
 Ability to replicate for extended periods of time
 Growth regulators and control mechanisms
 Self renewal by similar pathways
 Stimulation of angiogenesis through secretion of
angiopoietic factors
 Expression of similar surface receptors (e.g.
CD34, CD38 in case of leukemia)

19. Do CSCs Arise From Stem
Cells?
• Given the similarities between tumor-
initiating cells and stem cells, researchers
have sought to determine whether CSCs
arise from stem cells, progenitor cells, or
differentiated cells present in adult tissue.

21. Identification of CSCs in the
hematopoietic system

22. Solid tumor CSC’s

23. Conclusion
• The discovery of CSCs in some tumor
types has ushered in a new era of cancer
research.
• Therapeutic strategies against multiple
malignancies have severe limitations as it
is resistance to chemotherapy and
radiotherapy.
“Like a plate of poisoned cookies from
Grandma, cancer could be coming from
an unlikely place.”

24. References
• https://stemcells.nih.gov/info/Regenerative_Medicine/2006chapter9.
htm#ref16
• https://med.stanford.edu/ludwigcenter/overview/theory.html
• Gupta K, Gulen F, Sun L, Aguilera R, Chakrabarti A, Kiselar J, et al.
GSK3 is a regulator of RAR-mediated differentiation. Leukemia
2012;26(6):1277-85.
• Gu X, Hu Z, Ebrahem Q, Crabb JS, Mahfouz RZ, Radivoyevitch T, et
al. Runx1 regulation of Pu.1 corepressor/coactivator exchange
identifies specific molecular targets for leukemia differentiation
therapy. The Journal of biological chemistry 2014;289(21):14881-95.
• Logtenberg, M.E.W., and Boonstra, J. (2013). Cancer stem cells and
addicted cancer cells. Oncol Discov 1, 7.
• Topcul, M., Topcul, F., and Cetin, I. (2013). Asian Pacific Journal of
Cancer Prevention 14, 2819-2822.