Table 2.

Extracellular matrix–vesicle interaction.

Scene	Events	Ref.
1. Around producer cells	a. CAFs and cancer cells are major producers of matrix proteins.	[51,52]
	b. EVs are embedded within ECM and accumulated around producer cells.	[70]
	c. EVs and ECM mutually promote their accumulation around cells.	[70]
	d. sEVs act similar to car wheels to help cells migrate on rails of fibronectin.	[71]
	e. MMPs cleave matrix proteins to release matrix vesicles, growth factors, and chemokines.	[72]
	f. MMPs destroy ECM to increase the accessibility of proteins, EVs, and drugs to target cells.	[70]
2. In bodily fluids (or tissue culture supernatant)	a. EVs are often coated with matrix (fibronectin, proteoglycan, agrin, tenascin, hyaluronan).	[64,73]
	b. EV surface MMPs promote the dissemination of EVs.	[7]
3. At niches (at local and distant tissues)	a. EV surface integrins bind to ECM, leading to niche formation.	[74]
	b. EV surface matrices bind to ECM on the surface of recipient cells.	[75]
	c. EV surface growth factors, cytokines and chemokines determine uptake and bio distribution.	[76]
	d. MMPs loaded in EVs are transferred into recipient cell nuclei and transactivate the CCN2 gene, encoding a matricellular protein.	[7]
	e. EV surface MMPs promote the penetration of EVs into target tissues.	[8]