LIM and SH3 protein 1 (LASP1) differentiates malignant chordomas from less malignant chondrosarcomas

J Neurooncol. 2022 May;158(1):81-88. doi: 10.1007/s11060-022-04012-9. Epub 2022 May 4.

Abstract

Purpose: Chordomas are malignant tumors that develop along the neuraxis between skull-base and sacrum. Chondrosarcomas show similarities with chordomas, yet show less malignant behavior. LIM and SH3 protein 1 (LASP1) is a cytoskeletal protein known to promote the malignant behavior of tumors. LASP1 was previously identified as a possibly overexpressed protein in a chordoma proteomics experiment. In this study we compare LASP1 expression in chordoma and chondrosarcoma tissue.

Methods: Biopsies of primary tumors were collected from surgically treated chordoma (n = 6) and chondrosarcoma (n = 6) patients, flash-frozen upon collection and collectively analyzed for LASP1 RNA (real-time PCR) and protein expression (western blotting). Additionally, tissue micro array (TMA)-based immunohistochemistry was applied to an archive of 31 chordoma and 1 chondrosarcoma specimen.

Results: In chordoma samples, LASP1 mRNA was detected in 4/6 cases and a strong 36 kDa immunoreactive protein band was observed in 4/5 cases. In contrast, 0/6 chondrosarcoma samples showed detectable levels of LASP1 mRNA and only a weak 36 kDa band was observed in 4/5 cases. Immunohistochemical analysis showed LASP1 expression in all chordoma samples, whereas chondrosarcoma specimen did not show immunoreactivity.

Conclusion: LASP1 is strongly expressed in the majority of chordoma cases and shows low expression in chondrosarcoma tissue. Since LASP1 is known to function as oncogene and regulate cell proliferation in other tumor types, this study implicates a role for LASP1 in chordoma biology. Further studies are warranted to improve understanding of LASP1's expression and functioning within chordoma, both in vitro and in vivo.

Keywords: Chondrosarcoma; Chordoma; Expression; LASP1; Tissue microarray.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Chondrosarcoma* / genetics
  • Chondrosarcoma* / pathology
  • Chordoma* / metabolism
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism
  • Humans
  • Immunohistochemistry
  • LIM Domain Proteins / genetics
  • LIM Domain Proteins / metabolism
  • RNA, Messenger
  • Skull Base Neoplasms*

Substances

  • Adaptor Proteins, Signal Transducing
  • Cytoskeletal Proteins
  • LASP1 protein, human
  • LIM Domain Proteins
  • RNA, Messenger