Related Experiment Video
Updated: May 20, 2026
11:31
Determining Optimal Cytotoxic Activity of Human Her2neu Specific CD8 T cells by Comparing the Cr51 Release Assay to the xCELLigence System
Published on: August 8, 2012
Cellular effects of HER3-specific affibody molecules
Lovisa Göstring1, Magdalena Malm, Ingmarie Höidén-Guthenberg
1Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences, Uppsala University, Uppsala, Sweden.
Plos One
|July 7, 2012
Summary
Two Affibody molecules targeting the epidermal growth factor receptor HER3 blocked cancer cell growth. These HER3-specific molecules inhibited heregulin-induced signaling, showing promise for HER3-targeted cancer therapy.
Area of Science:
- Oncology
- Molecular Biology
- Biotechnology
Background:
- Epidermal growth factor receptor HER3 is increasingly recognized as a key target in cancer therapy.
- Previous research generated Affibody molecules with high affinity for HER3.
Purpose of the Study:
- To investigate the anti-cancer effects of two HER3-specific Affibody molecules, Z05416 and Z05417.
- To evaluate their ability to inhibit HER3 signaling and cancer cell proliferation.
Main Methods:
- Flow cytometry and confocal microscopy to confirm Affibody binding to HER3.
- Western blot analysis to assess downstream signaling pathways (Ras-MAPK, PI3K-Akt).
- In vitro proliferation assays to measure anti-proliferative effects.
Main Results:
- Affibody molecules Z05416 and Z05417 successfully bound to HER3 on cancer cell lines.
- They blocked the binding of the natural ligand heregulin (HRG).
- Suppressed HRG-induced HER3/HER2 phosphorylation and downstream signaling, inhibiting cancer cell growth.
Conclusions:
- Affibody molecules Z05416 and Z05417 demonstrate significant anti-proliferative effects on breast cancer cells.
- They inhibit HRG-induced HER3 phosphorylation and signaling pathways.
- These Affibody molecules represent promising candidates for HER3-targeted cancer therapeutics.
Related Concept Videos
02:57Targeted Cancer Therapies
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
There are several types of targeted therapies against specific...
02:38Mitogens and the Cell Cycle
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
01:15Receptor Downregulation in MVBs
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
01:22Target Cell Response to Hormones
Hormones intricately bind to receptors on the surface or within target cells, initiating a cascade of cellular responses.
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
01:17Intracellular Signaling Affects Focal Adhesions
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...