Tumor microenvironment Flashcards
What are the 4 types of skin cancer?
- Basal cell carcinoma
- Squamous cell carcinoma
- Melanoma
- Rare types of skin cancer
What are the risk factors of melanoma?
- Multiple benign or atypical nevi (cells)
- A previous melanoma
- Family history of melanoma
- Sun sensitivity (UV)
- Immunosuppressors
- UV exposure
What is the first step of getting a tumor?
Mutation; once mutated: bigger chance for more mutations (whole cascade)
Does metastasis make cancer lethal?
No; cancer can spread quickly and destroy tissue (secundary tissue but also original tissue), these are the consequences of metastasis, so the conseuences of metastasis make cancer letal
What are the benefits for tumors if you look at angiogenesis
Angiogenesis is the formation of new bloodvessels from existing ones. The benefits are that it brings the tumor oxygen and nutriets, but it also helps with metastasis.
What makes Hypoxia so dangerous in the context of angiogenesis
Bloodvessels sense hypoxia around the tumor: that is the first sign for angiogenesis. The hypoxia is due to tumors receiving less blood than what they need. The tumors cells also secrete VEGF. This all will lead to fast growing new bloodvessels to the tumor, and since it needs to be fast, the bloodvessels are more leaky. It also has unusual branches
What are the factors what play a role with hypoxia angiogenesis
Hypoxia is a trigger for HIF1a (TF) and helps transcribing VEGF (in tumor cell). Chemotaxis occur and endothelial cells present VEGFR (receptor for VEGF) (healthy cells). VEGF binds to the receptor and stimulates angiogenesis
So HIF1a, VEGF and VEGFR
Is blocking VEGF for cancer treatment convenient?
No, blocking VEGF may stop angiogenesis around tumor cells, but you will also block angiogenesis in healthy cells, since angiogenesis also occur in healthy tissues
What are the steps for tumor development + progression and metastasis?
1.Oncogenic induction (mutation)
2. Tumor formation
3. Angiogenesis
4. Tumor proliferation
5. Invasive cell release from primary tumor
6. Invasion/migration through basal membrane/movement
7. Intravasation: cells enter bloodstream/lymphatics
8. Cells survive in circulation
9. Extravasation: cells leave bloodstream/lymphatics
10. Survive in new tissue
11. Growth of metastasis: the development of secundary malignant tumors (more leaky)
Why is ALCAM highly expressed in the secreted cells in melanoma?
A theory: because of MMP’s; ALCAM might be a signal for MMP’s to cleave the way for tumors
What are the 2 interactions of ALCAM?
- Homophilic binding (ALCAM-ALCAM)
- Heterophilic binding (CD6)
Explain the influence of Keratinocyte on melanoma
Normal: melanocyte and keratinocyte interaction. Keratinocytes are in control of the melanocyte. 1 melanocyte can interact with tons of keratinocytes. Once the connection is lost, melanocytes start to misbehave. This might be the start of melanoma.
Melanoma cells need to escape from the control by keratinocytes. What are the 3 major mechanisms?
- Downregulation of receptors is important for communication with keratinocytes (ex. E-cadherin, P-cadherin, desmoglein and connexins)
- Upregulation of receptors and signaling molecules what are not found on normal melanocytes, but are important for melanoma-melanoma and melanoma-fibroblast interactions (ex. N-cadherin, ALCAM, C1CAM, Mel-CAM, ZO1)
- Loss of anchorage to the basement membrane because of an altered expression of the ECM binding integrin family
Explain the Seed and Soil theory by Sir Stephen Paget
Primary cancers have somehow a favourite secundary organ to metastasize to, so metastasis is not randomly across the body.
The seed is the cancer cells and the soil is the secundary organ
What makes up the tumor micro-environment
- Cancer cells
- Non cancer cells
- Secreted soluble factors
- Non-cellular solid material (ECM)
These cells and components are equally important
