Exosomes are small extracellular vesicles that play various roles in cancer. They can promote tumor growth, angiogenesis, and metastasis. Exosomes carry proteins, lipids, and nucleic acids that are exchanged between cancer cells and other cell types to influence the tumor microenvironment. They can also serve as biomarkers for cancer detection and may help predict treatment responses by mediating drug resistance. Additionally, exosomes show potential as a drug delivery system to target cancer cells.

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2. Role of Exosomes in cancer
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3. Contents:
• What are exosomes?
• Exosomal composition and functions
• Exosomal synthesis and secretion
• Uptake of Exosomes by recipient cells
• Exosomes as mediator of intracellular communication
• Exosomes and Cancer
i. Role in metastasis
ii. Role in angiogenesis
iii. Role in diagnosis
iv. Role in cancer therapy and drug resistance
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4. Introduction to exosomes:
• Exosomes are cell-derived vesicles present in almost all body
fluids including:
 Blood and serum
 Urine
 Breast milk and amniotic fluid
 Nasal secretions and CSF
 Cultured mediums of cell cultures
• Diameter is 30-100 nm.
• Encapsulated by a lipid bilayer.
• High concentration in circulation during pregnancy and cancer.
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Electron microscope image of exosomes
derived from bladder cancer cells
100nm

5. Composition:
Exosomes are composed of a wide range of contents including:
• Proteins ( integrins, selectins, Rab proteins, SNAREs, tetraspanins like
CD9, CD81, CD63 etc)
• Lipids (e.g, steroids, sphingolipids, glycerophospholipids)
• Nucleic acids (mRNA, miRNA, sRNA, DNA)
• Growth receptors
• Soluble factors
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6. Functions:
• Different biological functions both in normal and pathophysiological
conditions.
• Elimination of un-necessary proteins & molecules from cell and blood
coagulation.
• Exchange of materials between cells, intercellular communication.
• Propagation of pathogens, immune responses (inhibitory and regulatory),
Antigen presentation and many more….!!!
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7. Synthesis and Secretion:
The process of exosome biogenesis is divided into four stages
• Initiation
• Endocytosis
• Multivesicular bodies (MVBs) formation and
• Exosome secretion
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8. Uptake by recipient cell:
Recipient cells uptake exosomes by 3 mechanisms:
Through receptors:
• No specified receptors. Some molecules act like EUR including Tim1, Tim4,
ICAM-1.
Direct fusion with plasma membrane:
• Smallest amount studied mode of uptake.
• Malignant melanoma cells take up exosome by fusion with low H-ion
concentration which facilitate this process.
Phagocytosis:
• Most effective approach of exosomal uptake.
• For example, exosomes from PC12 cells
(rat pheochromocytoma) were internalized
through endocytosis.
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9. Intracellular communication:
• Exosomes play a vital role in cell to cell communication.
• They transfer proteins, ribonucleic acid and miRNA into
recipient cells.
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10. Exosomes and
cancer:
Cancer cells secrete
exosomes, that act in several ways:
Paracrine mode: release their miRNAs
on recipient neighboring cells, that
induce post-transcriptional repression
or activate membrane surface receptors
to favor growth and invasiveness.
Endocrine mode: come into circulation,
approach tissues at distant
organs, wherever they're pre-
occupied by recipient cells and
stimulates pathologic process.
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11. Role in metastasis:
• Pre-metastatic niche: Primary tumor cells release a variety of cytokines
and growth factors that firstly mobilizeand recruit bone-marrow- derived
cells (BMDCs) to the site of future metastasis, creating the permissive
environment for incoming tumor cells, that is called the pre-metastatic
niche.
• In addition to endothelial cells, exosomes also affect other cells viz,
fibroblasts, immune cells etc.
• Fibroblasts activated to myofibroblasts stimulates tumor growth,
vascularization and metastasis.
• Deregulation of extracellular matrix through glycoproteins and
metalloproteinases of cancer exosomes.
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12. Role in Angiogenesis:
• Angiogenesis is the formation of new blood vessels and it
is important in growth into distant site.
• Vescular endothelial growth factor (VEGF): secretion of VEGF causes
enhanced growth.
• Tetraspanins: that are enriched in exosomes, are found to contribute to
exosome-mediated angiogenesis.
• Epidermal growth factor receptor (EGFR):
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Fusion between epithelial
membrane and exosome via PS
mediated process.
Growth cells over-express
molecules like CD147 which
activate MMPs.
Degradation of basement
membrane, liberation of
angiogenic factors, cappillaries
formed.

13. Exosomes as biomarkers??
• Exosomes may provide an excellent biomarker to monitor the emergence,
progression, and prognosis of cancer, as well as the efficacy of treatment
regimes.
• Exosomes can be readily detected in tumor tissue, and can be found in
higher concentrations, both in tumor tissue, and the serum and plasma of
cancer patients.
Examples:
• The presence of nucleic acid in exosomes has been described as a
biomarker in glioblastoma patients via the identification of the disease-
specific EGF receptor transcript.
• In melanoma patients exosomes contain high levels of the proteins
Caveolin-1 and CD63.
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14. Cancer therapy:
• Exosomes regulate immune responses both in a negative as well as
positive way, i.e, to promote and to treat cancer.
• For example, in case of ovarian tumor if tumor-derived exosomes are
removed from circulation , immune responses generated which start
degrading cancer cells.
• Moreover, exosomes can also be used in selected combination with cancer
therapeutics and targeted to recipient cancer cells.
Drug resistance:
• The blood-brain barrier (BBB) essentially restricts therapeutic drugs from
entering into the brain. Brain endothelial cell derived exosomes can
deliver anticancer drug across the BBB for the treatment of cancer.
• In case of ovarian cancer, malignant neoplastic disease cells develop
resistance against drug cisplatin.
• Exosomes can also function to neutralize antibody-based drugs and help
to reduce the anti-body dependent cytotoxicity.
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