Related Experiment Video
Updated: Oct 4, 2025
06:26
Analysis of Side Population in Solid Tumor Cell Lines
Published on: February 23, 2021
4.5K
ALCAM regulates multiple myeloma chemoresistant side population
Fangfang Wang1, Zhang Dan1, Hongmei Luo1
1Department of Hematology, West China Hospital/State Key Laboratory of Biotherapy and Cancer Center, Sichuan University, Chengdu, China.
Cell Death & Disease
|February 11, 2022
Summary
Activated Leukocyte Cell Adhesion Molecule (ALCAM) inhibits multiple myeloma (MM) drug resistance by regulating the side population (SP) of cells. Targeting the Epidermal Growth Factor Receptor (EGFR) may enhance MM treatment efficacy.
Area of Science:
- Oncology
- Cell Biology
- Molecular Medicine
Background:
- Drug resistance remains a significant barrier to curing multiple myeloma (MM).
- Activated Leukocyte Cell Adhesion Molecule (ALCAM) has been identified as a prognostic factor in MM.
- ALCAM was previously shown to inhibit Epidermal Growth Factor (EGF)/Epidermal Growth Factor Receptor (EGFR)-initiated MM clonogenicity.
Purpose of the Study:
- To investigate the role of the ALCAM-EGF/EGFR axis in mediating drug resistance in MM.
- To elucidate the mechanisms by which ALCAM influences the drug-resistant side population (SP) in MM.
- To evaluate the therapeutic potential of targeting the EGFR pathway in MM.
Main Methods:
- Investigated the ratio of SP cells in ALCAM-knockdown MM cells under various conditions (BMSCs, EGF).
- Assessed the drug resistance of SP MM cells to melphalan and bortezomib.
- Examined the effect of EGFR activation and ALCAM on the hedgehog pathway and SP-genesis.
- Analyzed mitochondrial function in SP MM cells and its role in SP-genesis.
- Conducted animal studies using combination therapy with an anti-MM agent and gefitinib.
Main Results:
- ALCAM knockdown increased the SP cell ratio in MM, particularly with bone marrow stromal cells or EGF.
- SP MM cells demonstrated resistance to melphalan and bortezomib, and drug treatment promoted SP-genesis.
- EGFR activation, stimulated by EGF, promoted SP ratio via the hedgehog pathway, while ALCAM inhibited pro-MM cell signaling.
- SP MM cells had increased mitochondria, and interfering with mitochondrial function inhibited SP-genesis.
- Combination therapy with an anti-MM agent and gefitinib prolonged survival in MM-bearing mice.
Conclusions:
- ALCAM acts as a novel negative regulator of drug resistance in multiple myeloma.
- The ALCAM-EGF/EGFR signaling axis is crucial in regulating MM drug resistance via the SP.
- EGFR inhibitors, such as gefitinib, represent a promising therapeutic strategy to improve MM treatment outcomes.
Related Concept Videos
02:57Targeted Cancer Therapies
7.9K
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...
There are several types of targeted therapies against...
7.9K
02:56Treatment Resistant Cancers
3.4K
Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.4K
02:50Combination Therapies and Personalized Medicine
5.1K
Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
5.1K