Autophagy in osteosarcoma

Janice Santiago O'Farrill1, Nancy Gordon

  • 1Department of Pediatrics-Research, The Children's Cancer Hospital, University of Texas M.D. Anderson Cancer Center, Houston, TX, 77030, USA.

Insights

Autophagy influences chemotherapy resistance in osteosarcoma lung metastases. Inhibiting autophagy increased gemcitabine sensitivity in human cells but decreased it in mouse cells, highlighting varied roles.

Area of Science:

  • Oncology
  • Cell Biology
  • Pharmacology

Background:

  • Osteosarcoma (OS) lung metastasis exhibits resistance to conventional chemotherapy, posing a significant clinical challenge.
  • Autophagy, a cellular self-degradation process, is implicated in tumor resistance to various chemotherapeutic agents.
  • Previous work demonstrated aerosol gemcitabine (GCB) efficacy in OS lung metastases, yet a subset of cells remains unresponsive.

Purpose of the Study:

  • To investigate the role of autophagy in chemotherapy resistance in osteosarcoma lung metastases.
  • To evaluate the impact of autophagy modulation on gemcitabine (GCB) sensitivity in different osteosarcoma cell lines.

Main Methods:

  • Assessment of autophagy induction by GCB in human (LM7) and murine (K7M3) metastatic OS cells.
  • Evaluation of GCB sensitivity following autophagy inhibition in both cell lines.
  • Analysis of in vivo therapeutic efficacy of GCB in OS lung metastases.

Main Results:

  • GCB treatment induced autophagy in both LM7 and K7M3 osteosarcoma cells.
  • Inhibition of autophagy enhanced GCB sensitivity in LM7 human cells.
  • Conversely, autophagy inhibition decreased GCB sensitivity in K7M3 murine cells.

Conclusions:

  • Autophagy plays a differential role in mediating chemotherapy response in osteosarcoma lung metastases.
  • Understanding these varied roles is crucial for developing targeted therapeutic strategies against OS metastasis.
  • Further research is needed to define optimal approaches for modulating autophagy in cancer therapy.

Related Concept Videos

Autophagy01:27

Autophagy

Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
5.0K
Delivery Pathways to the Lysosome01:36

Delivery Pathways to the Lysosome

Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
7.6K
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
3.3K
Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized...
3.9K
Osteoclasts in Bone Remodeling01:31

Osteoclasts in Bone Remodeling

Osteoclasts are cells responsible for bone resorption and remodeling. They originate from hematopoietic progenitor cells present in the bone marrow. Numerous progenitor cells fuse to form multinucleated cells, each with 10-20 nuclei. A single osteoclast has a diameter of 150 to 200 µM. These cells have ruffled borders that break down the underlying bone tissue and release minerals such as calcium into the blood in bone resorption. Osteoclasts cling to bones with their ruffled edges during...
3.9K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.6K