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Research group - Göran Andersson

A major part of our research involves investigating the role of tartrate resistant acid phosphatase (TRAP) in carcinogenesis, bone and adipose tissue development. We also study other aspects of e.g. bone metabolism and development with a special focus on the bone resorbing cell the osteoclast.

TRAP and cancer development

Increased TRAP is found in several primary malignant tumours, including breast, ovary and melanoma and often links to increased mortality. Therefore, we are studying the molecular mechanism behind the effect of TRAP in cancer development as well as characterizing new TRAP inhibitors. We have shown that TRAP increases the proliferation, migration and invasion of cancer cells and that this is associated with extracellular matrix and cell adhesion modulations.

Loading for strengthening the ageing skeleton (Sara Windahl PI)

Osteoporosis-related fractures constitute a major health concern and result in a huge economic burden on health care systems and much suffering to the patients. Mechanical loading as a result of load bearing physical activity, and estrogen receptor (ER) signalling are major regulators of bone mass. We and others have demonstrated that the bone anabolic response to mechanical loading is mediated via ERs. The molecular mechanisms for the crucial role of ERs for these effects are mainly unknown.

TRAP isoforms as biomarkers of different conditions

TRAP exists as two isoforms 5a and 5b. Both has been proposed as biomarkers for different cell types and conditions. TRAP 5b is used as marker for osteoclasts while TRAP 5a has been suggested to be a marker for inflammation. However, it has not been possible previously to measure TRAP 5a and 5b in the same sample. Therefore, we have recently developed a double TRAP 5a/5b protein sandwich ELISA enabling measurement of TRAP 5a and 5b in the same sample in co-operation with Mabtech AB. This gives us a new tool to study the potential of TRAP 5a and/or 5b as biomarkers.

TRAP in adipose tissue and obesity

Overexpression of TRAP leads to non-inflammatory hyperplastic obesity in mice due to increased proliferation and differentiation of new adipocytes. Also, in obese humans TRAP is elevated. We have shown that TRAP is secreted from adipose tissue macrophages and act on pre-adipocytes to increase proliferation and differentiation. Thus, TRAP and/or its receptor may be an interesting target to explore in different adipose tissue related disorders, including obesity and anorexia.

TRAP as a marker for distinct populations of tissue-resident and inflammatory macrophages

In addition to investigating the effect of TRAP on other cell types we are also studying the effect of TRAP on macrophages which expresses both TRAP 5a and TRAP 5b. I order to better understand the role of TRAP we are characterizing the phenotype of TRAP 5a+, TRAP 5b+ and TRAP- macrophages in different conditions e.g. smoke exposed mice lungs in a collaboration project.

Research group leader Göran Andersson

Group members

Pernilla Lång

Lecturer
H5 Department of Laboratory Medicine

Sara Windahl

Lecturer
H5 Department of Laboratory Medicine

Barbro Ek-Rylander

Senior researcher
H5 Department of Laboratory Medicine

Maria Norgård

Laboratory technician
H5 Department of Laboratory Medicine

Selected publications

Tartrate-resistant acid phosphatase (TRAP/ACP5) promotes metastasis-related properties via TGFβ2/TβR and CD44 in MDA-MB-231 breast cancer cells.
Reithmeier A, Panizza E, Krumpel M, Orre LM, Branca RMM, Lehtiö J, et al
BMC Cancer 2017 Sep;17(1):650

Identification of inhibitors of Tartrate-resistant acid phosphatase (TRAP/ACP5) activity by small-molecule screening.
Reithmeier A, Lundbäck T, Haraldsson M, Frank M, Ek-Rylander B, Nyholm PG, et al
Chem Biol Drug Des 2018 07;92(1):1255-1271

Identification of inhibitors of Tartrate-resistant acid phosphatase (TRAP/ACP5) activity by small-molecule screening.
Reithmeier A, Lundbäck T, Haraldsson M, Frank M, Ek-Rylander B, Nyholm PG, et al
Chem Biol Drug Des 2018 07;92(1):1255-1271

A Novel Sandwich ELISA for Tartrate-Resistant Acid Phosphatase 5a and 5b Protein Reveals that Both Isoforms are Secreted by Differentiating Osteoclasts and Correlate to the Type I Collagen Degradation Marker CTX-I In Vivo and In Vitro.
Mira-Pascual L, Patlaka C, Desai S, Paulie S, Näreoja T, Lång P, et al
Calcif. Tissue Int. 2020 Feb;106(2):194-207

The adipokine tartrate-resistant acid phosphatase 5a in serum correlates to adipose tissue expansion in obesity.
Patlaka C, Mira Pascual L, Paulie S, Henriksson AF, Arner P, Lång P, et al
Biomarkers 2017 Dec;22(8):764-774

Monomeric tartrate resistant acid phosphatase induces insulin sensitive obesity.
Lång P, van Harmelen V, Rydén M, Kaaman M, Parini P, Carneheim C, et al
PLoS ONE 2008 Mar;3(3):e1713

Transgenic overexpression of tartrate-resistant acid phosphatase is associated with induction of osteoblast gene expression and increased cortical bone mineral content and density.
Gradin P, Hollberg K, Cassady AI, Lång P, Andersson G
Cells Tissues Organs (Print) 2012 ;196(1):68-81

Caveolae-mediated endocytosis of the glucosaminoglycan-interacting adipokine tartrate resistant acid phosphatase 5a in adipocyte progenitor lineage cells.
Patlaka C, Norgård M, Paulie S, Nordvall-Bodell A, Lång P, Andersson G
Biochim. Biophys. Acta 2014 Mar;1843(3):495-507