In
cellular biology
Cell biology (also cellular biology or cytology) is a branch of biology that studies the Anatomy, structure, Physiology, function, and behavior of cell (biology), cells. All living organisms are made of cells. A cell is the basic unit of life th ...
, angiopellosis (cell
extravasation) is the movement of
cells out of the
circulatory system
In vertebrates, the circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the body. It includes the cardiovascular system, or vascular system, that consists of the heart ...
, into the surrounding tissue. This process is specific to non-leukocytic cells;
white blood cell
White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...
s (leukocytes) employ
diapedesis
In immunology, leukocyte extravasation (also commonly known as leukocyte adhesion cascade or diapedesis – the passage of cells through the intact vessel wall) is the movement of leukocytes (white blood cells) out of the circulatory system ( ex ...
for movement out of circulation. Angiopellosis was discovered by studying the way that
stem cell
In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can change into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type of cell ...
s reach damaged tissue when injected or infused into the circulatory system.
It has been found that
circulating tumor cells (CTCs) possess this ability to exit blood vessels through angiopellosis during the process of
metastasis
Metastasis is a pathogenic agent's spreading from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, ...
.
Angiopellosis involves
cell–cell recognition by the blood vessel wall (
endothelial cells
The endothelium (: endothelia) is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the res ...
), and the active
remodeling of the blood vessel to allow the cell to exit.
Mechanism
Angiopellosis extravasation occurs as a means for cells that are not native to the circulation to exit. This includes adult stem cells that are injected
intravenously
Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutr ...
for therapies. Cells that are normally found in circulation (i.e.
blood cell
A blood cell (also called a hematopoietic cell, hemocyte, or hematocyte) is a cell produced through hematopoiesis and found mainly in the blood. Major types of blood cells include red blood cells (erythrocytes), white blood cells (leukocytes), ...
s) either extravasate through diapedesis (white blood cells), or do not extravasate and remain in circulation (
red blood cell
Red blood cells (RBCs), referred to as erythrocytes (, with -''cyte'' translated as 'cell' in modern usage) in academia and medical publishing, also known as red cells, erythroid cells, and rarely haematids, are the most common type of blood cel ...
s).
Angiopellosis was first observed by researchers studying the mechanism by which intravenously injected
stem cells
In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can change into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type of cell ...
arrived at damaged tissue.
They discovered that the injected stem cells prompted the blood vessel walls to undergo extensive changes at the cellular level, resulting in the removal of the cell from within the vessel (
lumen) into the surrounding tissue.
Below is a brief summary of each of the steps currently thought to be involved in ''angiopellosis'':
Upon entering the circulation, the cell (or clump of cells) travels through the circulatory system and eventually attaches to or becomes lodged within the blood vessel wall. This prompts a series of events that ends with the cell exiting circulation:
#The endothelial cells of the vessel recognize the cell through
membrane-specific recognition. Recognition of the cell is vital, and is thought to be what prevents cells native to the circulation from randomly extravasating via angiopellosis.
#Once attached or lodged, the exiting cell(s) elicit activity from the endothelial cells of the blood vessel: the endothelial cells extend
protrusions and actively remodel themselves around the exiting cells.
#The exiting cell will then be either actively "pushed" from the inside of the blood vessel, or the vascular cells will remodel around the cell so that the cell no longer remains inside the vessel.
Differences from Leukocyte Extravasation
The most notable difference is the physical mechanism the cells use to exit. During ''angiopellosis'', the endothelial cells are the most active in the process, while in diapedesis it is the white blood cell that are the most physically active during the process.
During angiopellosis the extravasating cell remains round in morphology and only slightly changes shape as a result of the vasculature remodeling around it; during diapedesis, the white blood cells significantly change shape as they squeeze between the cells of the blood vessel wall.
Angiopellosis allows for the extravasation of multiple cells during a single event. The blood vessel will actively remodel around a cluster/group of cells and allow the cells to exit in a single event. Diapedesis only allows for a single white blood cell to migrate across the blood vessel wall at a given time. Although multiple white blood cells can leave simultaneously, they all elicit separate diapedesis extravasation events.
There are further temporal and molecular difference between the two processes.
Role in the Cancer Exodus Hypothesis
Angiopellosis is a critical component of the
Cancer Exodus Hypothesis, which posits that
circulating tumor cells (CTCs) can extravasate as multicellular clusters rather than only as single cells. According to this hypothesis, CTC clusters maintain their cohesive structure throughout the process of metastasis, which enhances their
metastatic potential.
This hypothesis challenges traditional views that CTC clusters must dissociate to initiate metastasis. Studies show that these clusters are capable of exiting blood vessels through angiopellosis while maintaining their multicellular configuration, thus enhancing their ability to establish secondary tumors. This cluster-based migration and extravasation may contribute to the increased
treatment resistance observed in metastases, as CTC clusters can harbor a greater diversity of cell types than single CTCs.
The Cancer Exodus Hypothesis underscores the importance of CTC clusters as biomarkers in
liquid biopsy techniques, as their presence can be indicative of advanced metastatic disease and cancer aggressiveness.
Stem cell infusion therapy
Stem cell infusion therapy is a type of
infusion therapy in which stem cells are infused into the blood. These stem cells then exit the blood vessels and preferentially migrate to damaged tissue as part of the regeneration process. Angiopellosis has been shown to be the mechanism by which stem cells extravasate and reach damaged tissue
See also
*
Leukocyte extravasation
In immunology, leukocyte extravasation (also commonly known as leukocyte adhesion cascade or diapedesis – the passage of cells through the intact vessel wall) is the movement of leukocytes (white blood cells) out of the circulatory system (ext ...
*
Endothelium
The endothelium (: endothelia) is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the r ...
*
Circulatory system
In vertebrates, the circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the body. It includes the cardiovascular system, or vascular system, that consists of the heart ...
References
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Cell movement