Cancer Biology UARK

Yuuchun Du

Cellular definition of Cancer is

a group of diseases in which abnormal cells proliferate without control and can invade nearby tissues.

Genetic definition of Cancer is

a type of genetic diseases, resulting from mutations.

Major sources of gene mutations:

➢ DNA replication
➢ Endogenous cellular biochemical factors
➢ Exogenous factors (carcinogens)

A tumor is:

An abnormal mass of tissue formed by an abnormal
growth of cells: benign or malignant; multicellular

Cancer is:

Malignant; single cell or multicellular

Classification of tumors

Primary tumor, Metastasis, Benign, Malignant

(Neolplasm=Tumor; neoplasia, new growth)

Primary tumor:

The original tumor

Metastasis:

Formed by cancer cells that have
spread from other part of the body

Benign tumor:

Grow locally without invading adjacent tissues

Malignant:

What type of tumor has invaded nearby tissues

Cancer classification, carcinomas:

Squamous cell carcinomas and Adenocarcinomas make up 80%

Cancer classification, Non-epithelial cancers:

Sarcomas: 1%, Leukemia/Lymphomas: 7%, Neuroectodermal tumors: 2.5%

Carcinomas:

Derive from epithelial cells; responsible for >80% the cancer-related deaths.

-Squamous cell carcinomas: From protective epithelial cells

-Adenocarcinomas: From secretory epithelial cells

Sarcomas:

Derive from mesenchymal cells; responsible for
~1% of tumors in the clinic

Leukemia/Lymphomas:

Derive from blood-forming
(hematopoietic) cells; responsible for ~7% of cancer-related
death.

Neuroectodermal tumors:

Derive from nervous system;
responsible for ~2.5% of cancer-related death.

The journey to malignancy:

1. Normal: normal appearance, normal division, and normal assembly
2. Hyperplasia: normal appearance, abnormal division, and normal assembly
3. Metaplasia: normal appearance, normal division, and abnormal assembly
4. Dysplasia: abnormal appearance, abnormal division, and abnormal assembly

5. Locally invasive tumors: abnormal appearance, abnormal division, abnormal assembly, and invasion to adjacent tissues
6. Metastases: abnormal appearance, abnormal division, abnormal assembly, invasion to adjacent tissues, and spread to other organs

5 hows of cancer:

➢ Tumors seem to develop progressively.
➢ Tumors are monoclonal growth.
➢ Cancer cells exhibit an altered energy metabolism.
➢ Specific physical, chemical, or viral agents induce cancers.
➢ The great majority of the commonly occurring cancers are caused by environmental factors.

Warburg effect:

The observation that most cancer cells obtain their energy from glycolysis, even in the presence of abundant O2

Cancer-causing agents are:

physical, chemical, or viral agents

Carcinogens vs. mutagens rule

➢ All mutagens are carcinogens
➢ Not all carcinogens are mutagens

Factors that contribute to cancer development:

-Heredity.
-Environment

Incidence rates:

The rates with which the disease is diagnosed. Cancer incidence rates are dramatically different among different populations.

The great majority of the commonly occurring
cancers are caused by

environment factors
- Physical environment: air, water, sunlight, etc
- Lifestyle: dietary choices, reproductive habits, tobacco usage, etc.

Basics of viruses

➢ A sub-microscopic infectious agent
(10-300 nm in diameter).
➢ Unable to grow or reproduce outside
a host cell (bacteria, plants, or animals).
➢ Structure: genome (DNA or RNA)
wrapped in a protein coat (capsid)

Anchorage independence:

Cells grow without attachment to the
solid substrate.

Tumorigenicity:

The ability of cultured cells to give rise to either benign
or malignant progressively growing tumors in in immunologically
nonresponsive animals.

Provirus:

The DNA version of the viral genome.

Retrovirus:

A single-stranded positive-sense RNA virus
with a DNA intermediate in the host cells.

Oncogene:

A gene capable of transforming a normal
cell into a tumor cell

Proto-oncogene:

The precursor of an active oncogene

what do the terms mean: src, c-src: , v-src

src is an additional gene found in RSV. cellular src , viral src

Why was the discovery of c-src gene a milestone in cancer research

➢ The concept of proto-oncogene implied that:
— the genomes of normal cells carry genes that have the potential to induce cancer.
— Other tumor viruses may convert other proto-oncogenes into oncogenes using a similar mechanism.
— The proto-oncogene can be activated by other mechanisms than virus
➢ There might be many more other proto-oncogenes.
➢ c-src is the first proto-oncogene discovered.

Insertional mutagenesis:

Activation of cellular proto-oncogene by inserting provirus near the proto-oncogene

Three types of retroviruses that induce cancers

➢ Carry no oncogenes [e.g., avian leukosis virus (ALV)]; induce cancers slowly (weeks to months) through insertional mutagenesis.
➢ Carry acquired oncogenes [e.g., Rous sarcoma virus (RSV)]; induce cancers rapidly (days to weeks)
➢ Carry endogenous viral oncogenes [e.g., human T-cell leukemia virus (HTLV-I)]

Tumor viruses are generally either

➢ DNA viruses [e.g.,SV-40]
➢ Retroviruses