Yonsei Med J.  2014 Nov;55(6):1484-1488. 10.3349/ymj.2014.55.6.1484.

Autophagy Activity in Pulmonary Metastatic Tumor Tissues from Colorectal Cancer: A Pilot Study

• Kim YS
• Shin JH
• Bae MK
• Lee CY
• Kim DJ
• Chung KY
• Lee JG

• KMID: 2070194
• DOI: http://doi.org/10.3349/ymj.2014.55.6.1484

Abstract

PURPOSE
Autophagy has been reported to be involved in treatment failure in tumor. We aimed to evaluate autophagy activity in tumor tissue and compare them between the recurrence and non-recurrence groups.
MATERIALS AND METHODS
We analyzed expressions of autophagy-related proteins in tumor tissues which were obtained from pulmonary metastases of colorectal cancer patients by Western blot. We also analyzed autophagosomes by transmission electron microscopy.
RESULTS
Tumor tissues from recurrence group showed increased levels of LC3B-II, decreased levels of p62/SQSTM1, and also a marked accumulation of autophagosomes compared with tissues from non-recurrence group.
CONCLUSION
The present study suggests that autophagy may be associated with treatment failure of metastatic colorectal cancer.

Keyword

Colorectal cancer; metastasis; treatment failure; autophagy

MeSH Terms

Adaptor Proteins, Signal Transducing
Aged
*Autophagy
Blotting, Western
Colorectal Neoplasms/*metabolism/*pathology
Female
Humans
Lung Neoplasms/*metabolism/*pathology
Male
Microfilament Proteins/*metabolism
Microscopy, Electron, Transmission
Microtubule-Associated Proteins
Middle Aged
Neoplasm Recurrence, Local
Pilot Projects
Proteins
Retrospective Studies
Treatment Failure
Tumor Markers, Biological/metabolism
Adaptor Proteins, Signal Transducing
Microfilament Proteins
Microtubule-Associated Proteins
Proteins
Tumor Markers, Biological

Figure

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  Fig. 1 Increased autophagy activity (LC3II) correlates with treatment failure of pulmonary metastasis in colorectal cancer patients. (A) Western blot analysis for LC3B-II protein in tumors of CRC patients. The levels of LC3B-II were higher in tumor tissues from patients who had experienced recurrence than tissues from patients who had no recurrence. (B) Expression intensity of Western blot was measured by image J program. The data are mean±SEM (*p<0.05). CRC, colorectal cancer; SEM, standard error of mean.

• 

  Fig. 2 Decreased p62/SQSTM1 correlates with treatment failure of pulmonary metastasis in colorectal cancer patients. (A) Western blot analysis for p62/SQSTM1 in tumors of CRC patients. The p62/SQSTM1 expressions of tumor tissue from patients who had experienced recurrence showed trends of lower levels than tissues from patients who had no recurrence. (B) Expression intensity of Western blot was measured by image J program. The data are mean±SEM (p=0.201). CRC, colorectal cancer; SEM, standard error of mean.

• 

  Fig. 3 Autophagy activity (LC3II) of peri-tumor tissue shows no difference between no recurrence and recurrence group. (A) Western blot analysis for LC3B-II protein in peri-tumors of CRC patients. The levels of LC3B-II were not different in both no recurrence and recurrence group. (B) Expression intensity of Western blot was measured by image J program. The data are mean±SEM (p=0.797). CRC, colorectal cancer; SEM, standard error of mean.

• 

  Fig. 4 Autophagy vacuoles in tumor tissue from pulmonary metastasis in colorectal cancer patients by electron microscopy. (A) Electron micrographs showing ultrastructure of tumor tissue. Arrows indicate double-membraned autophagic vacuoles (magnification, ×20000). (B) Quantification of autophagic vacuoles in tumor cells was performed. The number of autophagic vacuoles in each cell was counted. The data are mean±SEM (*p<0.05). N, no recurrence; R, recurrence; SEM, standard error of mean.

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