Progression and Metastasis of Lung Cancer

Overview

Journal Cancer Metastasis Rev

Specialty Oncology

Date 2016 Mar 29

PMID 27018053

Citations 256

Authors

Helmut H Popper

Affiliations

Soon will be listed here.

Abstract

Metastasis in lung cancer is a multifaceted process. In this review, we will dissect the process in several isolated steps such as angiogenesis, hypoxia, circulation, and establishment of a metastatic focus. In reality, several of these processes overlap and occur even simultaneously, but such a presentation would be unreadable. Metastasis requires cell migration toward higher oxygen tension, which is based on changing the structure of the cell (epithelial-mesenchymal transition), orientation within the stroma and stroma interaction, and communication with the immune system to avoid attack. Once in the blood stream, cells have to survive trapping by the coagulation system, to survive shear stress in small blood vessels, and to find the right location for extravasation. Once outside in the metastatic locus, tumor cells have to learn the communication with the "foreign" stroma cells to establish vascular supply and again express molecules, which induce immune tolerance.

Citing Articles

Exosome tropism and various pathways in lung cancer metastasis.

Chen H, Liu L, Xing G, Zhang D, A N, Huang J Front Immunol. 2025; 16:1517495.

PMID: 40028322 PMC: 11868168. DOI: 10.3389/fimmu.2025.1517495.

[F]FDG PET/CT versus [F]FDG PET/MRI in staging of non-small cell lung cancer: a head-to-head comparative meta-analysis.

Yu D, Chen C Front Med (Lausanne). 2025; 11:1517805.

PMID: 39871837 PMC: 11769939. DOI: 10.3389/fmed.2024.1517805.

The Role of Pentacyclic Triterpenoids in Non-Small Cell Lung Cancer: The Mechanisms of Action and Therapeutic Potential.

Lee Y, Kwon R, Lee H, Chung J, Kim Y, Jeong H Pharmaceutics. 2025; 17(1).

PMID: 39861671 PMC: 11768946. DOI: 10.3390/pharmaceutics17010022.

Long non-coding RNA CAR10 promotes angiogenesis of lung adenocarcinoma by mediating nuclear LDHA to epigenetically regulate VEGFA/C.

Ge X, Du C, Fang L, Xu W, Xiang J, Liu J Commun Biol. 2025; 8(1):32.

PMID: 39789173 PMC: 11718007. DOI: 10.1038/s42003-025-07452-x.

Squamous cell carcinoma predicts worse prognosis in stage IA (≤ 2 cm) non-small cell lung cancer patients following sublobectomy: a population-based study.

Xu J, Zhang K, Chen H, Wu W, Li X, Huang Y Sci Rep. 2024; 14(1):30998.

PMID: 39730612 PMC: 11681023. DOI: 10.1038/s41598-024-81965-z.

References

Garcia-de-Alba C, Becerril C, Ruiz V, Gonzalez Y, Reyes S, Garcia-Alvarez J . Expression of matrix metalloproteases by fibrocytes: possible role in migration and homing. Am J Respir Crit Care Med. 2010; 182(9):1144-52. DOI: 10.1164/rccm.201001-0028OC. View

Bleckmann A, Siam L, Klemm F, Rietkotter E, Wegner C, Kramer F . Nuclear LEF1/TCF4 correlate with poor prognosis but not with nuclear β-catenin in cerebral metastasis of lung adenocarcinomas. Clin Exp Metastasis. 2012; 30(4):471-82. PMC: 3616220. DOI: 10.1007/s10585-012-9552-7. View

Tang C, Tan T, Fu W, Yang R . Involvement of matrix metalloproteinase-9 in stromal cell-derived factor-1/CXCR4 pathway of lung cancer metastasis. Carcinogenesis. 2007; 29(1):35-43. DOI: 10.1093/carcin/bgm220. View

Westhoff B, Colaluca I, dArio G, Donzelli M, Tosoni D, Volorio S . Alterations of the Notch pathway in lung cancer. Proc Natl Acad Sci U S A. 2009; 106(52):22293-8. PMC: 2799768. DOI: 10.1073/pnas.0907781106. View

Gil-Bernabe A, Ferjancic S, Tlalka M, Zhao L, Allen P, Im J . Recruitment of monocytes/macrophages by tissue factor-mediated coagulation is essential for metastatic cell survival and premetastatic niche establishment in mice. Blood. 2012; 119(13):3164-75. DOI: 10.1182/blood-2011-08-376426. View

Putora P, Ess S, Panje C, Hundsberger T, van Leyen K, Plasswilm L . Prognostic significance of histology after resection of brain metastases and whole brain radiotherapy in non-small cell lung cancer (NSCLC). Clin Exp Metastasis. 2015; 32(2):143-9. DOI: 10.1007/s10585-015-9699-0. View

Im J, Fu W, Wang H, Bhatia S, Hammer D, Kowalska M . Coagulation facilitates tumor cell spreading in the pulmonary vasculature during early metastatic colony formation. Cancer Res. 2004; 64(23):8613-9. DOI: 10.1158/0008-5472.CAN-04-2078. View

Horak C, Steeg P . Metastasis gets site specific. Cancer Cell. 2005; 8(2):93-5. DOI: 10.1016/j.ccr.2005.07.013. View

Boussat S, Eddahibi S, Coste A, Fataccioli V, GOUGE M, Housset B . Expression and regulation of vascular endothelial growth factor in human pulmonary epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2000; 279(2):L371-8. DOI: 10.1152/ajplung.2000.279.2.L371. View

10.

Kim B, Sohn E, Jung J, Shin E, You O, Im J . Inhibition of ZNF746 suppresses invasion and epithelial to mesenchymal transition in H460 non-small cell lung cancer cells. Oncol Rep. 2013; 31(1):73-8. DOI: 10.3892/or.2013.2801. View

11.

Wang C, Su Y, Zhang L, Wang M, You J, Zhao X . The function of SARI in modulating epithelial-mesenchymal transition and lung adenocarcinoma metastasis. PLoS One. 2012; 7(9):e38046. PMC: 3458851. DOI: 10.1371/journal.pone.0038046. View

12.

Holopainen T, Saharinen P, DAmico G, Lampinen A, Eklund L, Sormunen R . Effects of angiopoietin-2-blocking antibody on endothelial cell-cell junctions and lung metastasis. J Natl Cancer Inst. 2012; 104(6):461-75. PMC: 3309130. DOI: 10.1093/jnci/djs009. View

13.

Hiratsuka S, Goel S, Kamoun W, Maru Y, Fukumura D, Duda D . Endothelial focal adhesion kinase mediates cancer cell homing to discrete regions of the lungs via E-selectin up-regulation. Proc Natl Acad Sci U S A. 2011; 108(9):3725-30. PMC: 3048115. DOI: 10.1073/pnas.1100446108. View

14.

Xu L, Xu W, Jiang Z, Zhang F, Chu Y, Xiong S . Depletion of CD4(+)CD25(high) regulatory T cells from tumor infiltrating lymphocytes predominantly induces Th1 type immune response in vivo which inhibits tumor growth in adoptive immunotherapy. Cancer Biol Ther. 2008; 8(1):66-72. DOI: 10.4161/cbt.8.1.7131. View

15.

Yen L, You X, Al Moustafa A, Batist G, Hynes N, Mader S . Heregulin selectively upregulates vascular endothelial growth factor secretion in cancer cells and stimulates angiogenesis. Oncogene. 2000; 19(31):3460-9. DOI: 10.1038/sj.onc.1203685. View

16.

Kothari S, Cizeau J, McMillan-Ward E, Israels S, Bailes M, Ens K . BNIP3 plays a role in hypoxic cell death in human epithelial cells that is inhibited by growth factors EGF and IGF. Oncogene. 2003; 22(30):4734-44. DOI: 10.1038/sj.onc.1206666. View

17.

Han L, Liang X, Chen L, Bao S, Yan Z . SIRT1 is highly expressed in brain metastasis tissues of non-small cell lung cancer (NSCLC) and in positive regulation of NSCLC cell migration. Int J Clin Exp Pathol. 2013; 6(11):2357-65. PMC: 3816804. View

18.

Wood S, Pernemalm M, Crosbie P, Whetton A . The role of the tumor-microenvironment in lung cancer-metastasis and its relationship to potential therapeutic targets. Cancer Treat Rev. 2013; 40(4):558-66. DOI: 10.1016/j.ctrv.2013.10.001. View

19.

Peng X, Guo W, Ren T, Lou Z, Lu X, Zhang S . Differential expression of the RANKL/RANK/OPG system is associated with bone metastasis in human non-small cell lung cancer. PLoS One. 2013; 8(3):e58361. PMC: 3596380. DOI: 10.1371/journal.pone.0058361. View

20.

Sadanandam A, Varney M, Kinarsky L, Ali H, Mosley R, Singh R . Identification of functional cell adhesion molecules with a potential role in metastasis by a combination of in vivo phage display and in silico analysis. OMICS. 2007; 11(1):41-57. DOI: 10.1089/omi.2006.0004. View