CANCER AND METASTASIS

Speaker :Sandeep kumar

Tumor Or Neoplasm An abnormal cell that grow and proliferate out of control

Benign Tumor As long as neoplastic cells do not become invasive

A Tumor is considered a Cancer only if it is malignant i.e.

Invasiveness is a essential characteristic of cancer cell

•More se l f - suff i c i en t then norma l ce l l s f o r g rowth and pro l i f e ra t i on

•I n sens i t i ve to an t i - p ro l i f e ra t i ve ex t race l l u l a r s i gna l s

•Less prone to undergo apoptos i s

•Defec t i ve i n i n t race l l u l a r con t ro l mechan i sms tha t norma l l y s top ce l l d i v i s i on permanen t l y i n r e sponse to s t r e ss o r DNA damage

•I nduce ang iogenes i s

•Metas tas i ze

•Gene t i ca l l y uns tab l e

•Ei ther p roduce te l omerase o r acqu i re o ther ways o f s t ab i l i z i ng the i r t e l omeres .

General Behaviors of Cancer Cell

Types of Cancer

Carcinoma - cancer that begins in the skin or in tissues that line or cover internal organs e.g. adenocarcinoma, basal cell carcinoma and transitional cell carcinoma.

Sarcoma - cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue.

Leukemia - cancer that starts in blood-forming tissue such as the bone marrow

Lymphoma and myeloma - cancers that begin in the cells of the immune system.

Central nervous system cancers - cancers that begin in the tissues of the brain and spinal cord.

Carcinogens

Any agent that provoke the development of cancer is called carcinogenic

Carcinogenesis is linked to the Mutagenesis(i.e. cause mutations)

Carcinogens are classified into 2 classes1) Chemical carcinogen: Typically cause simple

local changes in nucleotide sequence and2) Radiations such as x- Rays: Typically cause

chromosomal breakage and Translocation & UV Rays: Cause specific DNA base alteration

i.e. Point mutation

CANCER AND THE CELL CYCLE

In cancer cells CDK4 and CyclinD is either Mutated or over-expressed

A GENETIC BASIS FOR CANCER

Oncogene : genes whose products play important roles in the regulation of biochemical activities within cells, including those activities related to cell division

First discovered in the genomes of RNA viruses-called υ-onc

Later, the cellular counterparts of these viral oncogenes were discovered in many different organisms, ranging from Drosophila to humans called c-onc/normal celluar oncogene/proto-oncogene

Rous sarcoma virus: First tumor-inducing virus discovered in 1910 by Peyton Rous

Contains 4 different genes:Gag- which encodes the capsid protein of the

virion; pol-which encodes the reverse transcriptase; Env- which encodes a protein of the viral

envelope;v-src- which encodes a protein kinase that

inserts into the plasma membranes of infected cells, responsible for tumor formation

v-src gene produces 100 times as much tyrosine kinase as the c-src gene, oversupply of the kinase upsets the delicate signaling mechanisms that control cell division, causing unregulated growth

Structure of Rous Sarcoma Virus

MUTANT CELLULAR ONCOGENESAND CANCER

CHROMOSOME REARRANGEMENTS AND CANCER

Translocated chromosome9 22Philadelphia chromosome causes chronic myelogenous leukemia (CML)

The Tyrosine kinase function of the c-Ablprotein has been constitutively activated by the bcr/c-abl gene fusion

White blood cells grow and divide uncontrollably.

Tumor Suppressor Genes

Genes that are normally involved in the restraint of cell growth, also called anti-oncogenes

Molecular Biology of Cancer Cell

Molecular Biology of Cancer Cell

The pathway by which Rb controls cell cycle entry

Molecular Biology of Cancer Cell

This system becomes abnormally activated early in tumor progression

What is cancer metastasis?

Metastasis is the process by which a tumor cell leaves the primary tumor, travels to a distant site via the circulatory system, and establishes a secondary tumor

Metastatic tumors

Preferential metastatic sites

Primary tumor Common distant site (s)Breast’ adenocarcinoma Bone, brain, adrenal

Prostate adenocarcinoma Bone

Lung small cell carcinoma Bone, brain, liver

Skin cutaneous melanoma Brain, liver, Bowel

Thyroid adenocarcinoma Bone

Kidney clear cell carcinoma Bone, liver, thyroid

Testis carcinoma Liver

Bladder carcinoma Brain

Neuroblastoma Liver, adrenal

5 major steps in metastasis

1. Invasion and infiltration of surrounding normal host tissue with penetration of small lymphatic or vascular channels;

2. Release of neoplastic cells, either single cells or small clumps, into the circulation;

3. Survival in the circulation; 4. Arrest in the capillary beds of distant organs;5. Penetration of the lymphatic or blood vessel

walls followed by growth of the disseminated tumor cells.

Steps in the Process of Metastasis

Molecular Changes in Metastatic Cancer Cell

Over expression of Rho-family GTPase RhoC, mediate actin-based cell mobility

Epithelial to Mesenchymal transition: change in expression of E- cadherin gene,required for cell cell adhesion

Tumor induce Angiogenesis

To grow , a tumor needs an adequate blood supply to get sufficient O2 and nutrients so form new blood vessels(Angiogenesis), and lymphatic vessels (Lymphangiogenesis)

Hypoxia

HIF-1α(gene regulatory protein) VEGF(pro-angiogenic factor)

Attract endothelial cells and stimulate growth of new blood vesselsVessels not only supply nutrients & O2 but also provide escape

route forits cells to metastasize

Thank you