Cancer Stem Cells (Lecture 18)

Embryonic Stem Cells

• Pluripotent

• Produce all differentiated cell types in adult organisms

Adult Stem Cells

• Multipotent

• Some differentiated cell types

Hemaatopoietic Stem Cells (HSCs)

Less than 0.1% of bone marrow

Cancer Stem Cells (CSCs)

Specific tumor cells with specific characteristics

Originate from normal adult stem cells

Neural Stem Cells are mostly tied to

Gliomas

HSCs are mostly linked to

leukemia

Mammary stem cells are most linked to

Breast cancer

Stem Cells and Cancer Cells Similarities

• Proliferation

• High telomerase

• Decrease in apoptosis

• Less mutations required

• Only live long enough to get multilple mutations for malignancy

WNT

Colon cancer

Notch

Breast cancer

SHH

Brain cancer

Cancer cells and CSCs in Leukemia (AML)

CD34+, CD38-

Cancer cells and CSCs in Breast Cancer

CD44+, CD24-

Cancer Cells and CSCs : Brain cancer

CD33+

Normal No WNT

• Frizzled

• Inactive dishevelled

• AXIN/APC

• B-catenin

• No nucleus

• No stem cell proliferation

Normal WNT

• WNT present

• Frizzled

• Active Dishevelled

• NO AXIN/APC

• B-catenin translocate to nucleus and then transcripted to DNA

• Stem cell proliferation

Colon Cancer WNT

• Overexpression of WNT

• Overactive Dishevelled, frizzled

• Loss of APC/AXIN

• Increase B-catenin (mutation)

• Cancer cell proliferation

Therapeutics for WNT

TNIK inhibitor

TNIK inhibitor

DNA binding to B-catenin that produces transcription

CSC’s

• Resistant to treatment because of high levels of DNA repair

• Have transporters that can remove drugs from cells