krchristie
commented
3 years ago Here are some key quotes from the existing definition references for the terms podosome and invadopodium, plus a couple reviews, one from 2011 and another from 2020, that help to define and distinguish these two terms. Comments supporting the contention that invadopodium is out of scope for GO are bolded.
Reviews
Murphy DA, Courtneidge SA. The 'ins' and 'outs' of podosomes and invadopodia: characteristics, formation and function. Nat Rev Mol Cell Biol. 2011 Jun 23;12(7):413-26. PMID:21697900
- Typically, structures of this type are referred to as podosomes when they are found in normal cells and as invadopodia when they are found in cancer cells.
Maurin J, Blangy A, Bompard G. Regulation of invadosomes by microtubules: Not only a matter of railways. Eur J Cell Biol. 2020 Aug 21;99(7):151109. PMID:33070039
- Invadosomes, which encompass podosomes and invadopodia, are actin rich adhesive and protrusive structures facilitating invasion and migration in various cell types. Podosomes are mostly found in normal cells, while invadopodia are hallmarks of invasive transformed cells. Despite evident structural differences, both structures mostly rely on the same pathways for their formation and their activity.
Podosome definition references
1: Linder S, Kopp P. Podosomes at a glance. J Cell Sci. 2005 May 15;118(Pt 10):2079-82. doi: 10.1242/jcs.02390. PMID:15890982
- Podosomes are typically formed in cells of the monocytic lineage, such as macrophages (Lehto et al., 1982; Linder et al., 1999), osteoclasts (Marchisio et al., 1984) or (immature) dendritic cells (Burns et al., 2001). However, they can also be found or induced in a variety of other cell types, including smooth muscle cells (Gimona et al., 2003) and endothelial cells (Moreau et al., 2003; Osiak et al., 2005).
- By contrast, invadopodia are found in fibroblasts transformed with viral oncogenes encoding protein tyrosine kinases (Tarone et al., 1985) and in some malignant cell types (Buccione et al., 2004). Indeed, the first observation of podosome-type adhesions 25 years ago described such virally induced invadopodia (David-Pfeuty and Singer, 1980).
2: Linder S, Aepfelbacher M. Podosomes: adhesion hot-spots of invasive cells. Trends Cell Biol. 2003 Jul;13(7):376-85. doi: 10.1016/s0962-8924(03)00128-4. PMID:12837608
- [from Abstract] Podosomes are highly dynamic, actin-rich adhesion structures of monocyte-derived cells, certain transformed fibroblasts and carcinoma cells and have recently also been discovered in an increasing number of other cell types. Because they are found mainly in motile cells and control the activity of matrix metalloproteases, podosomes are thought to contribute to tissue invasion and matrix remodeling. Importantly, podosomes are physiologically relevant organelles because they can be found in ex vivo models of invasive cells.
- Interestingly, ‘invadopodia’ do not qualify as podosomes as they have a different organization [11], although they might be derived from podosome-like precursors. However, there is no stringent definition of invadopodia in the literature.
Invadopodium definition references
1: Caldieri G, Buccione R. Aiming for invadopodia: organizing polarized delivery at sites of invasion. Trends Cell Biol. 2010 Feb;20(2):64-70. PMID:19931459
- Recent years have witnessed growing interest in the biology of invadopodia, proteolytically active protrusions formed by invasive tumor cells when cultured on an extracellular matrix (ECM).
2: Caldieri G, Ayala I, Attanasio F, Buccione R. Cell and molecular biology of invadopodia. Int Rev Cell Mol Biol. 2009;275:1-34. PMID:19491051
- 3.1. Podosomes versus invadopodia
- Podosomes are highly dynamic, actin‐rich adhesion structures of monocyte‐derived cells. They are involved in the adhesion to, and perhaps movement on solid substrates, and consist of a densely packed actin core surrounded by a ring of components commonly found in focal adhesion structures (Gimona and Buccione, 2006, Gimona et al., 2008, Linder, 2007, Linder and Aepfelbacher, 2003). A picture has now emerged suggesting that podosomes represent physiologically relevant organelles that contribute to the linking of the cell membrane to solid surfaces, and may be relevant for tissue invasion and matrix remodeling by controlling focal degradation of ECM and activation of MMPs (Linder, 2007). Regulators of podosome formation, maintenance, and turnover include non‐RTKs like Src and focal adhesion kinase (FAK), Rho GTPases (mainly Rac1, RhoA, and Cdc42), a diverse set of actin cytoskeleton modulators, and also the microtubule and intermediate filament cytoskeletons. Of note, the role of the latter two is virtually unexplored for invadopodia. Recent work has demonstrated that epithelial cells, as well as vascular endothelial and smooth muscle cells can also form podosomes, and that they contain the same molecular complement as their monocytic counterparts (Hai et al., 2002, Osiak et al., 2005, Spinardi et al., 2004).
- It is thus evident that molecular, morphological, and functional parameters must be applied to distinguish podosomes from invadopodia. A clear, detailed framework has been provided to help make this distinction (Linder, 2007), which can be summarized in the following concepts. Podosomes are dynamic, rapidly turning‐over (2–12 min), small (1 × 0.4 mm), dot‐like structures organized in rings and/or distributed at the leading edge as opposed to the persistent (up to 3 h), larger (up to 8 × 5 mm), irregularly shaped invadopodia, which tend to be confined to the central area of cells. The latter are typically formed by cancer‐derived cells and are less numerous (1–10 per cell) as compared to podosomes (20–100 per cell), but more aggressive toward the substrate.
3: Ghersi G, Zhao Q, Salamone M, Yeh Y, Zucker S, Chen WT. The protease complex consisting of dipeptidyl peptidase IV and seprase plays a role in the migration and invasion of human endothelial cells in collagenous matrices. Cancer Res. 2006 May 1;66(9):4652-61. doi: 10.1158/0008-5472.CAN-05-1245. PMID:16651416
- DPP4 and seprase were coexpressed with the three major protease systems (matrix metalloproteinase, plasminogen activator, and type II transmembrane serine protease) at the cell surface and organize as a complex at invadopodia-like protrusions.
In these 3 papers used for the definition of invadopodium, the first two support the contention that invadopodium is out of scope of GO. The third one, Ghersi et al. 2006, actually seems to be characterizing normal biology, but never refers to these structures as invadopodia instead using the term invadopodia-like protrusions.
pgaudet
gthayman
In looking into this ticket: move podosome in hierarchy and create its own membrane term #20443, looking at the existing definition references for the terms
podosomeandinvadopodium, plus a couple reviews, one from 2011 and another from 2020, I thinkinvadopodiumis an abnormal structure found in cancerous or transformed cells that is out of scope of GO. I think we should obsolete these terms.I considered the idea that the invadopodium terms should be merge into/converted to the corresponding podosome terms. However, I think that is probably not a good idea based on this paper:
Linder S, Aepfelbacher M. Podosomes: adhesion hot-spots of invasive cells. Trends Cell Biol. 2003 Jul;13(7):376-85. doi: 10.1016/s0962-8924(03)00128-4. PMID:12837608
Here are the invadopodium terms that we have:
Here's a summary of the experimental annotations:
There are also sequenced based annotations. The 31 ISO ones are all for MGI and RGD, so largely what you would expect based on the orthology based transfers from human. There are also 32 ISS annotations by UniProt.