Amyloid precursor-like protein 2 suppresses irradiation-induced apoptosis in Ewing sarcoma cells and is elevated in immune-evasive Ewing sarcoma cells

Haley L. Peters, Ying Yan, Tara M. Nordgren, Christine E Cutucache, Shantaram S Joshi, Joyce C Solheim

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Despite surgery, chemotherapy, and radiotherapy treatments, the children, adolescents, and young adults who are diagnosed with metastasized Ewing sarcoma face a dismal prognosis. Amyloid precursor-like protein 2 (APLP2) has recently been implicated in the survival of cancer cells and in our current study, APLP2's contribution to the survival of Ewing sarcoma cells was examined. APLP2 was readily detected in all Ewing sarcoma cell lines analyzed by western blotting, with the TC71 Ewing sarcoma cells expressing the lowest level of APLP2 among the lines. While irradiation induces apoptosis in TC71 Ewing sarcoma cells (as we determined by quantifying the proportion of cells in the sub-G 1 population), transfection of additional APLP2 into TC71 decreased irradiation-induced apoptosis. Consistent with these findings, in parallel studies, we noted that isolates of the TC71 cell line that survived co-culture with lymphokine-activated killer (LAK) cells (which kill by inducing apoptosis in target cells) displayed increased expression of APLP2, in addition to smaller sub-G1 cell populations after irradiation. Together, these findings suggest that APLP2 lowers the sensitivity of Ewing sarcoma cells to radiotherapy-induced apoptosis and that APLP2 expression is increased in Ewing sarcoma cells able to survive exposure to cytotoxic immune cells.

Original languageEnglish (US)
Pages (from-to)752-760
Number of pages9
JournalCancer Biology and Therapy
Volume14
Issue number8
DOIs
StatePublished - Aug 1 2013

Fingerprint

Ewing's Sarcoma
Amyloid beta-Protein Precursor
Apoptosis
Radiotherapy
Lymphokine-Activated Killer Cells
Cell Line
Coculture Techniques
Population
Transfection
Young Adult
Cell Survival
Western Blotting
Drug Therapy

Keywords

  • Amyloid precursor-like protein 2
  • Cytotoxic
  • Ewing sarcoma
  • Immune evasion
  • Immunotherapy
  • Lymphokine-activated killer cell
  • Radiation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Molecular Medicine
  • Pharmacology

Cite this

@article{6757d67e9f5a48b5a0c9592084cedda8,
title = "Amyloid precursor-like protein 2 suppresses irradiation-induced apoptosis in Ewing sarcoma cells and is elevated in immune-evasive Ewing sarcoma cells",
abstract = "Despite surgery, chemotherapy, and radiotherapy treatments, the children, adolescents, and young adults who are diagnosed with metastasized Ewing sarcoma face a dismal prognosis. Amyloid precursor-like protein 2 (APLP2) has recently been implicated in the survival of cancer cells and in our current study, APLP2's contribution to the survival of Ewing sarcoma cells was examined. APLP2 was readily detected in all Ewing sarcoma cell lines analyzed by western blotting, with the TC71 Ewing sarcoma cells expressing the lowest level of APLP2 among the lines. While irradiation induces apoptosis in TC71 Ewing sarcoma cells (as we determined by quantifying the proportion of cells in the sub-G 1 population), transfection of additional APLP2 into TC71 decreased irradiation-induced apoptosis. Consistent with these findings, in parallel studies, we noted that isolates of the TC71 cell line that survived co-culture with lymphokine-activated killer (LAK) cells (which kill by inducing apoptosis in target cells) displayed increased expression of APLP2, in addition to smaller sub-G1 cell populations after irradiation. Together, these findings suggest that APLP2 lowers the sensitivity of Ewing sarcoma cells to radiotherapy-induced apoptosis and that APLP2 expression is increased in Ewing sarcoma cells able to survive exposure to cytotoxic immune cells.",
keywords = "Amyloid precursor-like protein 2, Cytotoxic, Ewing sarcoma, Immune evasion, Immunotherapy, Lymphokine-activated killer cell, Radiation",
author = "Peters, {Haley L.} and Ying Yan and Nordgren, {Tara M.} and Cutucache, {Christine E} and Joshi, {Shantaram S} and Solheim, {Joyce C}",
year = "2013",
month = "8",
day = "1",
doi = "10.4161/cbt.25183",
language = "English (US)",
volume = "14",
pages = "752--760",
journal = "Cancer Biology and Therapy",
issn = "1538-4047",
publisher = "Landes Bioscience",
number = "8",

}

TY - JOUR

T1 - Amyloid precursor-like protein 2 suppresses irradiation-induced apoptosis in Ewing sarcoma cells and is elevated in immune-evasive Ewing sarcoma cells

AU - Peters, Haley L.

AU - Yan, Ying

AU - Nordgren, Tara M.

AU - Cutucache, Christine E

AU - Joshi, Shantaram S

AU - Solheim, Joyce C

PY - 2013/8/1

Y1 - 2013/8/1

N2 - Despite surgery, chemotherapy, and radiotherapy treatments, the children, adolescents, and young adults who are diagnosed with metastasized Ewing sarcoma face a dismal prognosis. Amyloid precursor-like protein 2 (APLP2) has recently been implicated in the survival of cancer cells and in our current study, APLP2's contribution to the survival of Ewing sarcoma cells was examined. APLP2 was readily detected in all Ewing sarcoma cell lines analyzed by western blotting, with the TC71 Ewing sarcoma cells expressing the lowest level of APLP2 among the lines. While irradiation induces apoptosis in TC71 Ewing sarcoma cells (as we determined by quantifying the proportion of cells in the sub-G 1 population), transfection of additional APLP2 into TC71 decreased irradiation-induced apoptosis. Consistent with these findings, in parallel studies, we noted that isolates of the TC71 cell line that survived co-culture with lymphokine-activated killer (LAK) cells (which kill by inducing apoptosis in target cells) displayed increased expression of APLP2, in addition to smaller sub-G1 cell populations after irradiation. Together, these findings suggest that APLP2 lowers the sensitivity of Ewing sarcoma cells to radiotherapy-induced apoptosis and that APLP2 expression is increased in Ewing sarcoma cells able to survive exposure to cytotoxic immune cells.

AB - Despite surgery, chemotherapy, and radiotherapy treatments, the children, adolescents, and young adults who are diagnosed with metastasized Ewing sarcoma face a dismal prognosis. Amyloid precursor-like protein 2 (APLP2) has recently been implicated in the survival of cancer cells and in our current study, APLP2's contribution to the survival of Ewing sarcoma cells was examined. APLP2 was readily detected in all Ewing sarcoma cell lines analyzed by western blotting, with the TC71 Ewing sarcoma cells expressing the lowest level of APLP2 among the lines. While irradiation induces apoptosis in TC71 Ewing sarcoma cells (as we determined by quantifying the proportion of cells in the sub-G 1 population), transfection of additional APLP2 into TC71 decreased irradiation-induced apoptosis. Consistent with these findings, in parallel studies, we noted that isolates of the TC71 cell line that survived co-culture with lymphokine-activated killer (LAK) cells (which kill by inducing apoptosis in target cells) displayed increased expression of APLP2, in addition to smaller sub-G1 cell populations after irradiation. Together, these findings suggest that APLP2 lowers the sensitivity of Ewing sarcoma cells to radiotherapy-induced apoptosis and that APLP2 expression is increased in Ewing sarcoma cells able to survive exposure to cytotoxic immune cells.

KW - Amyloid precursor-like protein 2

KW - Cytotoxic

KW - Ewing sarcoma

KW - Immune evasion

KW - Immunotherapy

KW - Lymphokine-activated killer cell

KW - Radiation

UR - http://www.scopus.com/inward/record.url?scp=84881440028&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84881440028&partnerID=8YFLogxK

U2 - 10.4161/cbt.25183

DO - 10.4161/cbt.25183

M3 - Article

VL - 14

SP - 752

EP - 760

JO - Cancer Biology and Therapy

JF - Cancer Biology and Therapy

SN - 1538-4047

IS - 8

ER -