S100 is a family of calcium-binding proteins found in vertebrates that are characterized by two EF-hand calcium-binding sites. There are 21 members of the S100 family that are structurally similar but not functionally interchangeable. S100 proteins are produced by normal skin, salivary gland, fat, cartilage, and nerve cells, and tumors originating from these tissues may also produce S100. S100 proteins have a range of intracellular and extracellular functions through regulating calcium balance, cell apoptosis, migration, proliferation, differentiation, energy metabolism, and inflammation. Dysregulated expression of S100 proteins is common in cancers and contributes to tumorigenic processes.

1. All you need to know about S100 protein
What’s S100 protein?
The S100 proteins are a family of low molecular-weight proteins found in vertebrates
characterized by two calcium-binding sites that have helix-loop-helix ("EF-hand-type")
conformation. The S100 protein family is composed of 21 members that exhibit a high degree of
structural similarity, but are not functionally interchangeable.S100 family members function as
intracellular Ca2+ sensors and extracellular factors.S100 made by many different types of normal,
healthy cells including cells in the skin, salivary glands, fat, cartilage, and nerves. Tumours that
start from these types of tissue may also make S100. Once the S100 protein is made, it is held in
both the nucleus and cytoplasm of the cell. The nucleus is the part of the cell that holds most of
the cell’s genetic material (DNA) while the cytoplasm is the body of the cell that surrounds the
nucleus.
What does the S100 protein do?
The S100 proteins, a family of calcium-binding cytosolic proteins, have a broad range of
intracellular and extracellular functions through regulating calcium balance, cell apoptosis,
migration, proliferation, differentiation, energy metabolism, and inflammation.
Dysregulated expression of multiple members of the S100 family is a common feature of human
cancers, with each type of cancer showing a unique S100 protein profile or signature. Emerging in
vivo evidence indicates that the biology of most S100 proteins is complex and multifactorial, and
that these proteins actively contribute to tumorigenic processes such as cell proliferation,
metastasis, angiogenesis and immune evasion. Drug discovery efforts have identified leads for
inhibiting several S100 family members, and two of the identified inhibitors have progressed to

2. clinical trials in patients with cancer.
What types of tissues and cells that produce S100
Skin – Melanocytes and Langerhans cells
Salivary glands – Myoepithelial cells
Fat – Adipocytes
Cartilage – Chondrocytes
Nerves – Schwann cells
Brain and spinal cord – Glial cells
Lymph nodes – Dendritic cells
What does the S100 protein do?
The S100 proteins, a family of calcium-binding cytosolic proteins, have a broad range of
intracellular and extracellular functions through regulating calcium balance, cell apoptosis,
migration, proliferation, differentiation, energy metabolism, and inflammation.
What does S100 positive mean?
S-100 protein (S-100B) is the most widely used marker for peripheral nerve sheath tumors.
Although S-100 protein is positive in all benign Schwann cell tumors, this marker shows relatively
low sensitivity for MPNST (at most, around 50%).
Reference
1. Marenholz I, Heizmann CW, Fritz G (2004). "S100 proteins in mouse and man: from evolution
to function and pathology (including an update of the nomenclature)". Biochemical and

3. Biophysical Research Communications. 322 (4): 1111–22. doi:10.1016/j.bbrc.2004.07.096. PMID
15336958.
2. Memari B, Bouttier M, Dimitrov V, Ouellette M, Behr MA, Fritz JH, White JH (2015).
"Engagement of the Aryl Hydrocarbon Receptor in Mycobacterium tuberculosis-Infected
Macrophages Has Pleiotropic Effects on Innate Immune Signaling". Journal of Immunology. 195
(9): 4479–91. doi:10.4049/jimmunol.1501141. PMID 26416282.
3. Wilson, AJ; Maddox, PH; Jenkins, D (January 1991). "CD1a and S100 antigen expression in skin
Langerhans cells in patients with breast cancer". The Journal of Pathology. 163 (1): 25–30.
doi:10.1002/path.1711630106. PMID 2002421. S2CID 70911084.