Activated leukocyte cell-adhesion molecule (ALCAM) promotes malignant phenotypes of malignant mesothelioma

Our plain-English summary of Activated leukocyte cell-adhesion molecule (ALCAM) promotes malignant phenotypes of malignant mesothelioma, by F. Ishiguro, H. Murakami, T. Mizuno, et al (Journal of Thoracic Oncology, 2012).

The study

• Authors: F. Ishiguro, H. Murakami, T. Mizuno, M. Fujii, Y. Kondo, N. Usami, K. Yokoi, H. Osada, Y. Sekido
• Journal: Journal of Thoracic Oncology
• Published: 2012;7(5):890-9
• Cited by: 21 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: Cell-adhesion molecules play important roles involving the malignant phenotypes of human cancer cells. However, detailed characteristics of aberrant expression status of cell-adhesion molecules in malignant mesothelioma (MM) cells and their possible biological roles for MM malignancy remain poorly understood.

Methods: DNA microarray analysis was employed to identify aberrantly expressing genes using 20 MM cell lines. Activated leukocyte cell-adhesion molecule (ALCAM) expression in MM cell lines was analyzed with quantitative reverse transcription-polymerase chain reaction and Western blot analyses in 47 primary MM specimens with immunohistochemistry. ALCAM knockdown in MM cell lines was performed with lentivirus-mediated short hairpin RNA (shRNA) transduction. Purified soluble ALCAM (sALCAM) protein was used for in vitro experiments, whereas MM cell lines infected with the sALCAM-expressing lentivirus were tested for tumorigenicity in vivo.

Results: ALCAM, a member of the immunoglobulin superfamily, was detected as one of the most highly upregulated genes among 103 cell-adhesion molecules with microarray analysis. Elevated expression levels of ALCAM messenger RNA and protein were detected in all 20 cell lines. Positive staining of ALCAM was detected in 26 of 47 MM specimens (55%) with immunohistochemistry. ALCAM knockdown with shRNA suppressed cell migration and invasion of MM cell lines. Purified sALCAM protein impaired the migration and invasion of MM cells in vitro, and the infection of sALCAM-expressing virus into MM cells significantly prolonged survival periods of MM-transplanted nude mice in vivo.

Conclusion: Our study suggests that overexpression of ALCAM contributes to tumor progression in MM and that ALCAM might be a potential therapeutic target of MM.

In plain English

This laboratory study looked at a cell-surface protein called ALCAM in malignant mesothelioma. It did not study asbestos exposure. The authors compared 103 cell-adhesion genes across 20 mesothelioma cell lines and found that ALCAM was the second-highest scoring gene. All 20 cell lines had more than 4.5 times the ALCAM messenger RNA of an immortalized mesothelial cell line used for comparison, and 15 had more than 20 times. In 47 mesothelioma tumor specimens, 26 (55%) stained positive for ALCAM. ALCAM staining was not significantly related to tumor site or tissue type, nor to survival in the 22 patients with survival data. Reducing ALCAM in two cell lines cut cell migration and invasion by 30 to 50%, but did not affect cell proliferation. Adding a soluble form of ALCAM cut migration and invasion by 20 to 40%. Nude mice injected in the chest with mesothelioma cells that made soluble ALCAM survived significantly longer than control mice (p = 0.01). The authors concluded that ALCAM overexpression contributes to mesothelioma progression and that ALCAM might be a potential therapeutic target.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory study: gene and protein measurements in mesothelioma cell lines, tissue staining of tumor specimens, cell experiments reducing or adding ALCAM, and a mouse experiment
• Who was studied: 20 malignant mesothelioma cell lines, including 14 Japanese cell lines established in the authors' laboratory. 47 primary mesothelioma specimens: 35 pleura, 6 peritoneum and 6 other sites; 34 epithelial, 6 biphasic, 5 spindle, 1 desmoplastic and 1 lymphohistiocytoid. Of these, 28 came from patients at Japanese hospitals and 19 from a commercial US tissue array. Female nude mice were used for the animal experiment.
• Exposure: No asbestos exposure was studied. The experiments altered ALCAM: they reduced it with short hairpin RNA in mesothelioma cell lines, added it to MeT-5A mesothelial cells, and added soluble ALCAM (sALCAM) to cell cultures. In mice, the injected cells were engineered to produce sALCAM.
• Main results:
  • Among 103 cell-adhesion molecule genes analyzed in 20 mesothelioma cell lines, ALCAM was the second-highest scoring gene
  • All 20 mesothelioma cell lines expressed more than 4.5-fold ALCAM messenger RNA compared with the MeT-5A mesothelial cell line; 15 cell lines expressed more than 20-fold
  • In the 47 tumor specimens, 26 (55%) were ALCAM-positive (3+ or 2+); 9 (19%) scored 3+, 17 (36%) 2+, 14 (30%) 1+ and 7 (15%) 0
  • ALCAM staining showed no significant relationship with the site of origin or the histological subtype of the tumors
  • Among the 22 patients with survival data, no significant association was found between ALCAM expression and survival
  • Reducing ALCAM caused 30 to 50% inhibition of cell migration and invasion in both tested cell lines (NCI-H290 and Y-MESO-27); it did not affect cell proliferation
  • Adding ALCAM to MeT-5A mesothelial cells increased their migration and anchorage-independent growth but not their invasion
  • Adding purified soluble ALCAM to mesothelioma cell cultures caused 20 to 40% inhibition of cell migration and invasion
  • Nude mice injected with NCI-H290 cells producing soluble ALCAM survived significantly longer than mice injected with control (GFP) cells (p = 0.01, log-rank test); the number of mice is not stated in the text
• The authors' conclusion: The authors concluded that their study suggests ALCAM overexpression contributes to tumor progression in malignant mesothelioma and that ALCAM might be a potential therapeutic target
• Limitations the authors state:
  • The authors state that the mechanisms by which ALCAM enhances migration, invasion and anchorage-independent growth still need investigation
  • A proposed mechanism (MMP-2 inactivation) could not be confirmed in mesothelioma cells with reduced ALCAM

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Immunohistochemistry.

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