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Laminin I mediates resistance to lapatinib in HER2-positive brain metastatic breast cancer cells in vitro.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2024 Aug 06; Vol. 720, pp. 150142. Date of Electronic Publication: 2024 May 18. - Publication Year :
- 2024
-
Abstract
- The role of extracellular matrix (ECM) prevalent in the brain metastatic breast cancer (BMBC) niche in mediating cancer cell growth, survival, and response to therapeutic agents is not well understood. Emerging evidence suggests a vital role of ECM of the primary breast tumor microenvironment (TME) in tumor progression and survival. Possibly, the BMBC cells are also similarly influenced by the ECM of the metastatic niche; therefore, understanding the effect of the metastatic ECM on BMBC cells is imperative. Herein, we assessed the impact of various ECM components (i.e., Tenascin C, Laminin I, Collagen I, Collagen IV, and Fibronectin) on brain metastatic human epidermal growth factor receptor 2 (HER2)-positive and triple negative breast cancer (TNBC) cell lines in vitro. The highly aggressive TNBC cell line was minimally affected by ECM components exhibiting no remarkable changes in viability and morphology. On the contrary, amongst various ECM components tested, the HER2-positive cell line was significantly affected by Laminin I with higher viability and demonstrated a distinct spread morphology. In addition, HER2-positive BMBC cells exhibited resistance to Lapatinib in presence of Laminin I. Mechanistically, Laminin I-induced resistance to Lapatinib was mediated in part by phosphorylation of Erk 1/2 and elevated levels of Vimentin. Laminin I also significantly enhanced the migratory potential and replicative viability of HER2-positive BMBC cells. In sum, our findings show that presence of Laminin I in the TME of BMBC cells imparts resistance to targeted therapeutic agent Lapatinib, while increasing the possibility of its dispersal and clonogenic survival.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Subjects :
- Humans
Cell Line, Tumor
Female
Triple Negative Breast Neoplasms pathology
Triple Negative Breast Neoplasms metabolism
Triple Negative Breast Neoplasms drug therapy
Tumor Microenvironment drug effects
Cell Survival drug effects
Extracellular Matrix metabolism
Extracellular Matrix drug effects
Lapatinib pharmacology
Lapatinib therapeutic use
Laminin metabolism
Drug Resistance, Neoplasm drug effects
Brain Neoplasms metabolism
Brain Neoplasms secondary
Brain Neoplasms drug therapy
Brain Neoplasms pathology
Receptor, ErbB-2 metabolism
Antineoplastic Agents pharmacology
Breast Neoplasms pathology
Breast Neoplasms metabolism
Breast Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 720
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 38788545
- Full Text :
- https://doi.org/10.1016/j.bbrc.2024.150142