Role of the small leucine-rich proteoglycan (SLRP) family in pathological lesions and cancer cell growth

J Nippon Med Sch. 2005 Jun;72(3):137-45. doi: 10.1272/jnms.72.137.


The roles of lumican, a member of the small-leucine-rich-proteoglycan (SLRP) family, in pathological fibrosis, cancer tissues and tumor cell growth were reviewed. Lumican is predominantly localized in the areas of pathological fibrosis including the thickened intima of human coronary arteries, ischemic and reperfused hearts, and acute pancreatitis and chronic pancreatitis (CP)-like lesions adjacent to pancreatic cancer nests. In these lesions, lumican mRNA and protein were transiently and ectopically overexpressed in most of the vascular smooth muscle cells (VSMCs) that migrated into the thickened intima, myocardial cells adjacent to an ischemic lesion, acinar cells, islet cells and fibroblasts of pathological pancreatic tissues. The low expression level of lumican in breast cancer is associated with rapid progression and poor survival. Lumican mRNA in breast cancer is overexpressed in fibroblasts adjacent to cancer cells but not in cancer cells. Furthermore, the high expression level of lumican is associated with a high pathological tumor grade, a low estrogen receptor level in the cancer tissues, and young age of patients. The suppression of lumican expression in culture cells induces their cell growth. Lumican-transfected tumor cells are characterized by a strong suppression of their anchorage-independent growth and capacity of invasion. Lumican significantly suppressed subcutaneous tumor formation in syngenic mice, with a concomitant decrease in cyclin D1 expression level, and induced and/or enhanced the apoptosis of these cells. The autocrine mechanism in cancer cells and the paracrine mechanism in cancer cells and fibroblasts via transforming growth factor (TGF)-beta and Smad signals may play important roles in the regulation of tumor growth by SLRPs.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cell Communication / genetics
  • Cell Division / genetics*
  • Chondroitin Sulfate Proteoglycans / genetics
  • Chondroitin Sulfate Proteoglycans / physiology*
  • DNA-Binding Proteins / physiology
  • Fibrosis / genetics*
  • Gene Expression
  • Humans
  • Keratan Sulfate / genetics
  • Keratan Sulfate / physiology*
  • Lumican
  • Mice
  • Muscle, Smooth, Vascular / metabolism
  • Neoplasm Invasiveness / genetics
  • Neoplasm Staging
  • Neoplasms / pathology*
  • RNA, Messenger / metabolism
  • Smad Proteins
  • Trans-Activators / physiology
  • Transforming Growth Factor beta / physiology


  • Chondroitin Sulfate Proteoglycans
  • DNA-Binding Proteins
  • LUM protein, human
  • Lum protein, mouse
  • Lumican
  • RNA, Messenger
  • Smad Proteins
  • Trans-Activators
  • Transforming Growth Factor beta
  • Keratan Sulfate