Week 11: Stem Cells and Cancer

Question 1

What two tissues are skin composed of?

Answer 1

epithelial and connective

Question 2

Describe the layers of skin

Answer 2

Epithelium of epidermis, loose connective tissue of dermis, dense connective tissue of dermis, fatty connective tissue of hypodermis.

Question 3

What does epidermis contain?

Answer 3

keratinocytes, pigment cells (melanocyte), Langerhans cell (immune response).

Question 4

What does loose connective tissue of dermis contain?

Answer 4

Macrophages, collagen fibers, fibroblasts, endothelial cell forming capillary, lymphocyte

Question 5

What does dense connective tissue of dermis contain?

Answer 5

Fibroblasts, collagen fiber, elastic fiber.

Question 6

What factors affecting tissue organization?

Answer 6

• cell communication - with other cells and environment
• selective cell adhesion - diff adhesion mechanisms help cells maintain correct position within the tissue
• cell memory - each cell type has gene expression memory to facilitate production of identical type of cell

Question 7

Describe stem cells

Answer 7

Stem cells generate a continuous supply of terminally differentiated cells. Each can self-renew (terminally differentiate). Different tissue are renewed at diff rates. They split to form self-renewing cells and proliferating precursor cells which then form terminally differentiated cells.

Question 8

Describe dicty development.

Answer 8

There is a projection zone followed by touch done zone. There are prestalk cells and prespore cells also.

Question 9

Describe renewal in epithelial lining of adult mammalian intestine.

Answer 9

Renewal occurs continuously in the epithelial lining of adult mammalian intestine. Crypts descend into underlying connective tissue. Stem cells lie at bottom of crypt. Proliferating precursor cells move upward in plane of epithelial sheet. Absorptive or secretory cells are shed into gut.

Question 10

Describe epidermis renewal

Answer 10

The epidermis is renewed from stem cells in basal layer. Dead cells are shed from epidermis and new cells are born in dermis.

Question 11

Describe hemopoietic stem cell

Answer 11

Many blood cells are derived from single type of stem cell. T and B lymphocytes, eosinophils, basophils, neutrophils, monocytes (form osteoclasts and macrophages), megakaryocytes (form platelets) and RBCs all are made from them.

Question 12

Describe stem cell signaling. Example: Wnt proteins

Answer 12

Specific signals maintain stem-cell populations - Wnt signaling pathway. Wnt proteins are secreted in and around crypt base to promote proliferation of stem cells.

Question 13

How do we indefinitely maintain stem cells in culture

Answer 13

Mouse embryonic stem cells can be maintained indefinitely as pluripotent stem cells in culture. When exposed to specific extracellular signals, they can differentiate into specific cell types.

Question 14

What are IPS cells good for?

Answer 14

Induced pluripotent stem (IPS) cells provide convenient source of human ES-like cells.

Question 15

What are 2 characteristics of cancer cells?

Answer 15

Cancer cells 1) proliferate excessively and 2) migrate inappropriately. Evolve to give competitive advantage.

Question 16

What are 3 was cancer-causing mutations cluster?

Answer 16

Cancer-causing mutations cluster in a few fundamental pathways: 1) alternations in cell proliferation 2) DNA damage response 3) cell growth

Question 17

What are 3 things cancer cells do?

Answer 17

Cancer cells proliferate, metastasize and invade. To metastasize - cells of primary tumour in epithelium must cross basal lamina, migrate through connective tissues and get into blood or lymphatic vessels.

Question 18

What mutations do cancer cells develop?

Answer 18

Cancer develops by accumulation of mutations - defects in DNA replication and repair, cell-cycle checkpoint mechanisms, mistakes in mitosis and abnormal chromosome numbers.

Question 19

How do cancer cells evolve?

Answer 19

Cancer cells evolve by repeated rounds of mutation, proliferation and NS. At each step, a single cell undergoes mutation that enhances ability to proliferate/survive so its progeny become dominant clone in tumor. Some cancers have multiple clones each with own set of mutations.

Question 20

What is the difference between benign and malignant tumours?

Answer 20

Benign - grow in confined local area - small nucleus, regular shape, low mitotic index, normal tissue organization, well differentiated and tumour well defined.

Malignant - invade surrounding tissues + spread - large nucleus, pleomorphic (irregular nuclear shape), high mitotic index, disorganized tissue, poor differentiation, poorly defined tumour boundary

Question 21

What are the two main classes of genes critical for cancer?

Answer 21

Two main classes of genes critical for cancer - oncogenes and tumor suppressor genes.

Proto-oncogenes (regulate processes cancer depends on) →(mutation) oncogene

Tumor suppressor gene →(mutation inactivates a copy) no →(mutation inactivates other copy) → eliminated gene

Question 22

How are proto-oncogenes converted into oncogenes?

Answer 22

Mutation in coding sequence leading to hyperactive protein, gene amplification leading to overproduction of protein, and chromosome rearrangement leading to nearby regulatory sequence causing protein overproduction or fusion to actively transcribed genes to produce hyperactive fusion proteins.

Question 23

What genetic effects can eliminate activity of tumour suppressor gene?

Answer 23

Loss of function mutation in tumour suppressor gene in maternal chromosome + Whole paternal chromosome lost, region containing normal gene deleted, loss of function mutation in paternal gene, gene activity silenced by epigenetic changes.

Question 24

Describe polyp formation

Answer 24

Loss of tumour suppressor gene APC results in formation of a polyp in colorectal cancer. Additional mutations can lead to colon cancer.
Normal epithelium -> (tumour suppressor gene APC lost) -> excessive epithelial proliferation ->(oncogene (Ras) activated) small tumour-> (another tumor suppressor gene lost) large tumour -> (third tumour suppressor gene p53 lost) tumor is invasive ->(rapid accumulation of other mutations) metastasis.

Question 25

What is role of APC protein in Wnt pathway?

Answer 25

The APC protein keeps Wnt signalling pathway inactive when cell is not exposed to Wnt protein.
Without the Wnt signal, the receptor is inactive,signalling protein is inactive, the APC-containing complex is active which degrades beta-catenin and the TCF complex is inactive - Wnt-responsive genes off.

With the Wnt signal, the Wnt protein activates the receptor which activates the signalling protein that deactivates the APC-containing complex, releasing beta-catening which activates TCF complex. This causes transcription of Wnt-responsive genes, leading to proliferation of gut stem cells.

Question 26

Summary

Answer 26

• Reduced dependence on cell signalling
• Resist stress levels that would cause normal cells to undergo apoptosis
• Genetically unstable
• Crave nutrients to make ATP
• Survive in abnormal locations
• Secrete signals that influence behaviour of normal cells in tissue.