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Peer-reviewedCC BY 4.0International Journal of Molecular Sciences

Hypoxic Microenvironment Effects on Matrix Metalloproteinases’ Expression and Enzymatic Activity, and HIFs’ Expression in Non-Small Cell Lung Cancer Cells

  • Georgina Gonzalez-Avila1
  • Cuauhtemoc Sandoval1
  • Bettina Sommer2
  • A. Armando Garcia-Hernandez3
  • Jose S. Lopez-Gonzalez4
  • Arnoldo Aquino-Gálvez5
  • Carina Becerril6
  • Edgar Flores-Soto7
7 affiliations
  1. 1Departamento de Investigación en Enfermedades Crónico Degenerativas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Calzada de Tlalpan 4502, Col. Sección XVI, Tlalpan, Mexico City 14080, Mexico
  2. 2Departamento de Investigación en Hiperreactividad Bronquial, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Calzada de Tlalpan 4502, Col. Sección XVI, Tlalpan, Mexico City 14080, Mexico
  3. 3Departamento de Biomedicina Molecular e Investigación Traslacional, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Calzada de Tlalpan 4502, Col. Sección XVI, Tlalpan, Mexico City 14080, Mexico
  4. 4Laboratorio de Cáncer Pulmonar, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Calzada de Tlalpan 4502, Col. Sección XVI, Tlalpan, Mexico City 14080, Mexico
  5. 5Laboratorio de Biología Molecular, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Calzada de Tlalpan 4502, Col. Sección XVI, Tlalpan, Mexico City 14080, Mexico
  6. 6Laboratorio de Biología Celular, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Calzada de Tlalpan 4502, Col. Sección XVI, Tlalpan, Mexico City 14080, Mexico
  7. 7Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, Coyoacán, Mexico City 04510, Mexico
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Abstract

The hypoxic tumor microenvironment (TME) promotes metastasis, in which matrix metalloproteinases (MMPs) play a central role. The present work aimed to analyze the effects of hypoxia on MMP expression and enzymatic activity, as well as hypoxia-inducible factor (HIF) expression in different non-small cell lung cancer (NSCLC) cells. Cells were cultured in 1% O2 for 6 and 12 h, and the effects of hypoxia on MMPs and HIFs were analyzed using Western blotting and zymography. The highest MMP-2 protein expression was detected in CALU-1 (p ≤ 0.003) and A549 cells (p ≤ 0.006) at 6 and 12 h, respectively. Higher levels of MMP-9 were detected in CALU-1 (p ≤ 0.003) at 6 h and in A549 cells (p ≤ 0.04) at 12 h. MMP-2 and MMP-9 had the highest enzymatic activity in SKMES-1 cells (p ≤ 0.003). Increased HIF-1α levels were detected in A427 (p ≤ 0.04) at 6 h and in SKLU-1 cells (p ≤ 0.01) at 12 h, while higher HIF-2α expression was found in SKMES-1 at 6 h and 12 h (p ≤ 0.04). In conclusion, although hypoxia induces changes in MMP-2 and MMP-9 expression in NSCLC cells through HIF-dependent or HIF-independent pathways, these effects are not necessarily similar to those observed in enzymatic activity and differ between cell lines.

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Cite

BibTeXRIS
BibTeX
@article{gonzalezavila2026hypoxic,
  title = {{Hypoxic Microenvironment Effects on Matrix Metalloproteinases’ Expression and Enzymatic Activity, and HIFs’ Expression in Non-Small Cell Lung Cancer Cells}},
  author = {Georgina Gonzalez-Avila and Cuauhtemoc Sandoval and Bettina Sommer and A. Armando Garcia-Hernandez and Jose S. Lopez-Gonzalez and Arnoldo Aquino-Gálvez and Carina Becerril and Edgar Flores-Soto},
  journal = {International Journal of Molecular Sciences},
  year = {2026},
  month = oct,
  doi = {10.3390/ijms27209314},
  url = {https://www.mdpi.com/1422-0067/27/20/9314},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Hypoxic Microenvironment Effects on Matrix Metalloproteinases’ Expression and Enzymatic Activity, and HIFs’ Expression in Non-Small Cell Lung Cancer Cells
AU  - Georgina Gonzalez-Avila
AU  - Cuauhtemoc Sandoval
AU  - Bettina Sommer
AU  - A. Armando Garcia-Hernandez
AU  - Jose S. Lopez-Gonzalez
AU  - Arnoldo Aquino-Gálvez
AU  - Carina Becerril
AU  - Edgar Flores-Soto
PY  - 2026
DA  - 2026/10/20
JO  - International Journal of Molecular Sciences
DO  - 10.3390/ijms27209314
UR  - https://www.mdpi.com/1422-0067/27/20/9314
AB  - The hypoxic tumor microenvironment (TME) promotes metastasis, in which matrix metalloproteinases (MMPs) play a central role. The present work aimed to analyze the effects of hypoxia on MMP expression and enzymatic activity, as well as hypoxia-inducible factor (HIF) expression in different non-small cell lung cancer (NSCLC) cells. Cells were cultured in 1% O2 for 6 and 12 h, and the effects of hypoxia on MMPs and HIFs were analyzed using Western blotting and zymography. The highest MMP-2 protein expression was detected in CALU-1 (p ≤ 0.003) and A549 cells (p ≤ 0.006) at 6 and 12 h, respectively. Higher levels of MMP-9 were detected in CALU-1 (p ≤ 0.003) at 6 h and in A549 cells (p ≤ 0.04) at 12 h. MMP-2 and MMP-9 had the highest enzymatic activity in SKMES-1 cells (p ≤ 0.003). Increased HIF-1α levels were detected in A427 (p ≤ 0.04) at 6 h and in SKLU-1 cells (p ≤ 0.01) at 12 h, while higher HIF-2α expression was found in SKMES-1 at 6 h and 12 h (p ≤ 0.04). In conclusion, although hypoxia induces changes in MMP-2 and MMP-9 expression in NSCLC cells through HIF-dependent or HIF-independent pathways, these effects are not necessarily similar to those observed in enzymatic activity and differ between cell lines.
SN  - 1422-0067
ER  -