Cancer Stem Cells

cancer stem cells

cells within a tumor

• self-renews

• give rise to heterogeneous populations of cells with different metabolic/mitotic activities + sensitivity to treatments

Explain the null hypothesis in a self-renewal test:

no difference among individual tumor cells in regard to their replication ability

Name methods to reject null hypothesis:

• using enzymes to separate cells from tumor

• count cells and cover dish with nutrients

• compare colony number to seeding number

• examine for any variation in colony size

How can tumor cells differ?

• some never replicate DNA (post-mitotic cells in permanent G0)

• some replicate VERY often 

• some infrequently replicate DNA (long G0)

What are consequences of different cell cycle times?

infrequently replicating cancer cells end up escaping treatment → tumor recurrence

Explain the cause of tumors:

high replication capacity cells with long cell cycle and very long G1 phase → mitosis yields cancer stem and TA cells → TA cells have limited replication and short cell cycle → loss of replication causes cells to be post-mitotic

What is the CSC theory?

• predicts clonal marker present during tumor expansion

• allows for heterogeneity despite shared marker

• read forward and reverse in time for cell identification

chronic myelogenous leukemia

diagnostically marked by chromosome rearrangements

• mutations might occur but all progeny share og mutation as marker

• if all cells have Philly chromosome, it can be clonally derived

Philadelphia chromosome

• translocation from 9 to 22

• characteristic length and banding pattern from staining chromosomes

• used to identify individual chromosomes

• if rearrangement share among progeny cells → clonal origin evidence

What happens if chemo drugs are able to kill off TA cell?

tumor shrinks but cancer stem cells survive → generates more cancer stem cells and TA cells → TA daughter cells replace tumor mass so now additional chemo is required to kill off new TA cells

How can therapeutics be improved to better target CSCs?

targeting over expressed receptors like EGF-R

• has 4 gene encoding related proteins: HER1, HER2, HER3, HER4

Describe the interaction between HER2 and therapeutic drugs:

• on breast cancer stem cells: very high HER2 levels, had frequent dimerization and kinase activation which drives mitosis → block kinase with erlotinib/gefitinib

• OR block dimerization with EGF-R with trastuzumab/cetuximab/panitumumab (antibody) → reduces ability to transmit growth signals into cell → less cell replication and tumor regression