1. Chapter 5 Neoplasia: A Disorder of Cell Proliferation and Differentiation

2. Neoplasia Neoplasms proliferate to form new tissue
They do not wait for signals from the body that the new tissue is needed
They ignore signals to stop dividing
They often do not mature normally (differentiate) to do the “job” the tissue is supposed to do
They do not die off (apoptosis) to keep the number of total cells constant

3. The Cell Cycle Labile cell M Permanent cell G2 Mitosis Inter-phase G1
Normally, the number of cells produced = the number of cells that die
The total number of cells in the body remains constant M
Permanent cell G2
Mitosis
Inter-phase G1 G0 S
Stable cell R

4. Growth Factors Labile cell M Permanent cell G2 Mitosis Inter-phase G1
Cells divide only when they are told to do so by growth factors
These cause stable cells to enter the cell cycle and divide M
Permanent cell G2
Mitosis
Inter-phase G1 G0 S
Stable cell affected by growth factors R

5. Growth Factors (cont.) Attach to receptor proteins 
Which often work by affecting G proteins 
Which turn on enzymes (proteins) 
Which make second messengers 
Which go down inside the cell and make it divide

6. A Cell Creates Proteins Based on Its Genes

7. Growth Factor Receptors
Now this cell is ready to respond to growth factors from another cell
They bind to the receptors and stimulate cell division

8. Proto-oncogenes
The normal genes that code for normal proteins used in cell division
Growth factors
Growth factor receptors
G proteins
Enzymes that produce second messengers
Genes that turn the production of these proteins on and off

9. Oncogenes Oncogenes are mutated proto-oncogenes
They still code for the proteins needed for cell division
But they might produce
Too much of the protein
An abnormal protein
Protein that turns on all by itself
Protein that is made when it is not needed
Protein that cannot turn cell division off
Protein that should be made by a different cell

10. Question Tell whether the following statement is true or false.
Oncogenes code for normal proteins used in cell division.

11. Answer
False
Rationale: The statement describes proto-oncogenes. Oncogenes are mutated proto-oncogenes that code for abnormal proteins.

12. This Cell Has Been Infected With a Cancer-causing Virus
What has changed?
How could it promote uncontrolled cell division?
What oncogene is to blame for this?

13. If You Want to Stop This Cell From Dividing, What Should You Do?
Give a drug that stops other cells from making the growth factor?
Give a drug that blocks the growth factor receptors?
Give a drug that inactivates growth factors in the extracellular fluid?

14. Here’s Another Cell with the Same Cancer—Would Any of These Treatments Work?
A drug that stops other cells from making the growth factor?
A drug that blocks the growth factor receptors?
A drug that inactivates growth factors in the extracellular fluid?

15. Checkpoints in Cell Division
Cyclins make sure the cell has made the proteins needed to separate the chromosomes M
Cyclin proteins measure whether the cell has grown large enough to divide
Permanent cell G2
Mitosis
Inter-phase G1 G0
Cyclins check that the DNA has been correctly duplicated S R

16. Tumor Suppressor Proteins
The checkpoints usually stop the division of mutated cells
They keep most mutations from developing into cancer
The proteins that control the checkpoints are called tumor suppressor proteins
Cyclins
Cyclin-dependent kinases
Cyclin inhibitors (p53)
If the genes for these proteins were mutated, you might get many more cancers

17. Cell Division Requires Duplicating the DNA
Telomeres: DNA sequences at the ends of the chromosomes
The enzymes that duplicate DNA attach here
The end of the telomere does not get duplicated
What will happen to the telomere as the cell continues dividing?
A man has a mutation that causes some of his cells to rebuild their telomeres after every division. Is this a good thing or a bad thing? Why?

18. Oncogenesis Initiation: initial mutation occurs
Promotion: mutated cells are stimulated to divide
Progression: tumor cells compete with one another and develop more mutations, which makes them more aggressive

19. Normal Cells Labile cell M Permanent cell G2 Mitosis Inter-phase G1 G0
Normally, after a cell has divided, it becomes either a permanent cell or a stable cell
These cells stop reproducing and continue working for the body M
Permanent cell G2
Mitosis
Inter-phase G1 G0 S
Stable cell R

20. Differentiation
“Grown-up” cells are called differentiated because they look different from one another
You can tell a spleen cell from a skin cell

21. Cell Mutation
When differentiated, “working” cells mutate, they form differentiated “working” tumors— benign tumors
When undifferentiated, rapidly dividing cells mutate, they form rapidly dividing tumors—malignant tumors

22. Question
When a well-differentiated cell mutates, is it more or less likely to become a malignant tumor?
More
Less
Degree of differentiation has no bearing on whether a tumor is malignant or benign.

23. Answer
b. Less
The more differentiated a cell is when it mutates, the more likely it is to become a benign tumor. If poorly differentiated cells mutate, the tumor is more likely to become malignant.

24. Naming Tumors Benign tumors: tissue name + “-oma”
Malignant tumors (cancers)
Epithelial tissue: tissue name + “carcinoma”
Mesenchymal tissue: tissue name + “sarcoma”

25. Benign Tumors Contain cells that look like normal tissue cells
May perform the normal function of the tissue (like secreting hormones)
This may lead to oversecretion
Usually have a capsule around them
Usually do not invade neighboring tissues
But they can damage nearby organs by compressing them

26. Benign Uterine Tumor With Clearly Defined Edges

27. Malignant Tumors
Contain cells that do not look like normal adult cells
These cells divide rapidly, so:
Tumors grow quickly
Cells mutate faster and can change type
The tumor does not have clear boundaries and sends “legs” out into surrounding tissue (the word cancer means “crab” and is based on these crablike legs)
Do not perform the normal functions of the organ
May secrete hormones associated with other tissues
Can compress and/or destroy the surrounding tissues

28. Malignant Lung Tumor Invades Surrounding Tissues

29. Question
What gross anatomic feature of the lung tumor you just saw makes it likely to be malignant?
The tumor is growing quickly.
The tumor has a poorly defined border.
Cells do not look like normal cells.
All of the above
b and c

30. Answer
b and c
Rationale: Gross anatomy can be viewed with the naked eye. Although rapid growth is a characteristic feature of malignant tumors, this cannot be determined from the slide. However, the lack of a clear border and the different appearance of the group of cancer cells can be clearly seen.

31. Metastasis
Cells in a primary tumor develop the ability to escape and travel in the blood
Imagine you were a cancer cell. What abilities would you need to survive in the tumor?
What abilities would you need to metastasize?

32. Scenario Mrs. T has liver cancer
Her doctor did an initial molecular diagnosis and put her on targeted therapy; the tumor shrank by almost 75%
Two years later the tumor was growing again, and this time it did not respond to the drug
Last year she was diagnosed with metastases in her femur that have not responded to the drug either
Mrs. T wants to know why the cancer cells stopped responding. Are they not all the same cells?

33. Manifestations of Cancer
Changes in organ function (organ damage, inflammation, and failure)
Local effects of tumors (e.g., compression of nerves or veins, gastrointestinal obstruction)
Ectopic hormones secreted by tumor cells (paraneoplastic disorders)
Nonspecific signs of tissue breakdown (e.g., protein wasting, bone breakdown)

34. Changes in Organ Function
Organ failure
Benign tumors may cause overproduction of normal organ secretions
Malignant tumors may occasionally cause overproduction (as in thyroid cancer), but more commonly decrease production of normal organ secretions

35. Question
Why do malignant tumors usually cause a reduction in the amount of hormones the affected organ produces?
Organ damage
Inflammation of the organ
Organ failure
All of the above
a and c

36. Answer
All of the above
Rationale: Effects of malignant tumors on the organ system include inflammation and damage, which ultimately lead to organ failure. In all cases the organ cannot function optimally, and is unable to secrete the normal/typical amount of hormones.

37. Local Effects of Tumor Growth
Bleeding
Compression of blood vessels
Superior vena cava syndrome
Portal hypertension
Compression of lymph vessels
Edema, ascites, effusion
Compression of hollow organs
Compression of nerves
Pain, paralysis

38. Paraneoplastic Syndromes
Cancer cells produce hormones or hormone-like proteins
ADH
ACTH
PTH-related protein
Cancer cells produce proteins that affect clotting
Paraneoplastic neurologic disorders

39. Generalized Effects of Cancer
Cancer cachexia syndrome
Weight loss
Muscle wasting
Weakness
Anorexia
Anemia