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Related Concept Videos

Complement System01:27

Complement System

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The complement system is a group of approximately 20 plasma proteins that strengthen the body's defenses against infections through opsonization, inflammation, and cell lysis. Opsonization involves coating pathogens with complement proteins, making them more recognizable and facilitating phagocyte engulfment. Certain complement proteins induce inflammation that attracts immune cells to the site of infection. Cell lysis involves the destruction of pathogens through the formation of a...
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Antimicrobial Proteins01:23

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Antimicrobial proteins are important components of the immune system. They aid the body in combating pathogens by either killing them directly or hindering their replication processes. Four main types of antimicrobial substances are interferons, the complement system, iron-binding proteins, and antimicrobial proteins.
Interferons
Interferons (IFNs) are proteins produced by lymphocytes, macrophages, and fibroblasts infected with viruses. While IFNs cannot prevent viruses from entering and...
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Defense Against Bacterial Pathogens01:31

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The human immune system is a complex network of cells, tissues, and organs that work together to defend the body against bacterial infections. It consists of various immune cells, each playing a specific role in the defense mechanism.
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Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
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Antibody Actions01:26

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Antibodies, or immunoglobulins, are critical players in the immune system's arsenal against invading pathogens. Produced by B cells and plasma cells, their primary role is to detect and bind to specific antigens, molecules found on the surface of pathogens like bacteria or viruses. Beyond antigen recognition, antibodies perform several vital functions that contribute to immune defense.
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Role of Proteins in the Human Body01:28

Role of Proteins in the Human Body

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Proteins are the building block of life. They are also  the most abundant macromolecules with as many diverse roles in the body. They are part of many structural components that provide unique shapes and structures to animal cells, tissues, and organs. In addition, they also act as biological catalysts and carry out several anabolic and catabolic reactions. Notably, some proteins are chemical messengers and regulate many critical processes, such as metabolism, growth, and development. They...
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Immunoglobulin-like Cell Adhesion Molecules01:31

Immunoglobulin-like Cell Adhesion Molecules

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Immunoglobulin-like cell adhesion molecules or Ig-CAMs are a versatile group of cell surface glycoproteins belonging to the immunoglobulin protein superfamily. Ig-CAMs possess the characteristic immunoglobulin protein domains and other domains such as the fibronectin type III domain. The Ig domains are glycosylated to varying degrees in different Ig-CAMs.
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Related Experiment Video

Updated: Aug 14, 2025

Evaluation of the Interplay Between the Complement Protein C1q and Hyaluronic Acid in Promoting Cell Adhesion
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Thinking inside the box: intracellular roles for complement system proteins come into focus.

Rebecca M O'Brien1,2, Niamh Lynam-Lennon1, Monica M Olcina3

  • 1Department of Surgery, Trinity St. James's Cancer Institute, Trinity Translational Medicine Institute, Trinity College Dublin, St. James's Hospital, Dublin 8, Ireland.

British Journal of Cancer
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PubMed
Summary

Complement anaphylatoxin C5a is generated intracellularly in colorectal cancer cells by cathepsin D, promoting tumor growth. Blocking C5a signaling halts tumorigenesis, revealing novel intracellular roles for complement proteins.

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Area of Science:

  • Immunology
  • Oncology
  • Molecular Biology

Background:

  • The complement system plays a role in cancer development.
  • Complement anaphylatoxin C5a is typically generated extracellularly.
  • Intracellular roles of complement proteins in cancer are emerging.

Purpose of the Study:

  • To investigate the intracellular generation of C5a in colorectal cancer.
  • To identify the enzyme responsible for intracellular C5 cleavage.
  • To determine the role of intracellular C5a in colorectal cancer progression.

Main Methods:

  • Analysis of colorectal cancer cells.
  • Identification of C5-cleaving enzymes.
  • Assessment of C5a signaling pathways.
  • Evaluation of C5a receptor blockade in tumorigenesis models.

Main Results:

  • C5 cleavage occurs intracellularly in colorectal cancer cells.
  • Cathepsin D was identified as the enzyme cleaving C5 into C5a.
  • Intracellular C5a stabilizes β-catenin through a KCTD5/cullin3/Roc-1 complex.
  • Blockade of C5a receptor 1 (C5aR1) inhibited tumor formation.

Conclusions:

  • Complement component C5 can be cleaved intracellularly in colorectal cancer.
  • Cathepsin D mediates C5 cleavage, producing functional C5a within cancer cells.
  • Intracellular C5a signaling contributes to colorectal cancer progression.
  • Targeting C5aR1 represents a potential therapeutic strategy for colorectal cancer.