Coordinator of Research Team
Name: Lido Calorini.
Position: Associate Professor in General Pathology
Name of Research Team/Laboratory …”Laboratory for heterotypic interactions in tumor microenvironment investigation”
telephone number: 390552751286; fax: 30055432431
Coordinator and team,
Brief biographical sketch of the Coordinator
Prof. Lido Calorini, born in S.Miniato (Pisa) 1953, Bachelor in Medicine and Surgery 1979, Residency in Haematology 1982, Ph.D in Experimental Pathology 1988 at the University of Florence, Associate Professor in General Pathology 2001.
Member of the scientific board of the Doctorate/PhD Program in
Genetics, Oncology and Clinical Medicine (GenOMeC), University of Siena, Director of the School Prof. A. Renieri
Member of the following Scientific Societies
1) Società Italiana di Patologia SIPMET
2) Istituto Toscano Tumori (ITT)
3) Unità di Ricerca n.12 “Ematologia e Oncologia Sperimentali” del “Excellence Center for Reasearch, Transfer and High Education DENOTHE, University of Florence
1) Francesca Bianchini, PhD in Clinical and Experimental Oncology, date of birth: 05/09/1971
2) Silvia Peppicelli, PhD in Biomedical Sciences (Clinical and Experimental Oncology),
date of birth: 10/04/1984
3) Elena Andreucci, PhD in Biochemistry and Molecular Biology, date of birth: 18/12/1987
Current research interests
Current topic of Prof. Calorini is the role exerted by extracellular acidosis generated by lactic acid release by tumor cells on malignant progression to a metastatic disease. The extracellular low pH drives in tumor cells a change in gene expression that is more profound than hypoxia. Prof. Calorini verified that acidosis influences plasticity of human melanoma cells and mesenchymal stem cells of tumor microenvironment conferring new properties useful for survival, local invasion and metastatic dissemination. Low pH also promotes in cancer cells a drug resistance that may be overcame using characteristic inhibitors. This leads to test whether pH-sensitive liposomes enriched in RGD might be used as a delivery nanocarriers of targeted agents.
Current / recent sources of funding
1) Istituto Toscano Tumori (ITT) : “Acidity in tumor environment: Molecular bases to interfere with malignant progression and cancer stem cells”. 2016-2018.
2) Fondi ex Ateno 2016-2017.
10 best publications of the last 5 years
1: Calvani M, Bianchini F, Taddei ML, Becatti M, Giannoni E, Chiarugi P, Calorini
L. Etoposide-Bevacizumab a new strategy against human melanoma cells expressing
stem-like traits. Oncotarget. 2016 Aug 9;7(32):51138-51149. doi:
10.18632/oncotarget.9939. PubMed PMID: 27303923; PubMed Central PMCID:
2: Peppicelli S, Toti A, Giannoni E, Bianchini F, Margheri F, Del Rosso M,
Calorini L. Metformin is also effective on lactic acidosis-exposed melanoma cells
switched to oxidative phosphorylation. Cell Cycle. 2016 Jul 17;15(14):1908-18.
doi: 10.1080/15384101.2016.1191706. PubMed PMID: 27266957; PubMed Central PMCID:
3: Peppicelli S, Bianchini F, Toti A, Laurenzana A, Fibbi G, Calorini L.
Extracellular acidity strengthens mesenchymal stem cells to promote melanoma
progression. Cell Cycle. 2015;14(19):3088-100. doi:
10.1080/15384101.2015.1078032. PubMed PMID: 26496168; PubMed Central PMCID:
4: Peppicelli S, Bianchini F, Calorini L. Metabolic reprogramming as a continuous
changing behavior of tumor cells. Tumour Biol. 2015 Aug;36(8):5759-62. doi:
10.1007/s13277-015-3762-y. PubMed PMID: 26159855.
5: Rovida E, Peppicelli S, Bono S, Bianchini F, Tusa I, Cheloni G, Marzi I,
Cipolleschi MG, Calorini L, Sbarba PD. The metabolically-modulated stem cell
niche: a dynamic scenario regulating cancer cell phenotype and resistance to
therapy. Cell Cycle. 2014;13(20):3169-75. doi: 10.4161/15384101.2014.964107.
PubMed PMID: 25485495; PubMed Central PMCID: PMC4612663. (Co-corresponding)
6: Peppicelli S, Bianchini F, Calorini L. Extracellular acidity, a
"reappreciated" trait of tumor environment driving malignancy: perspectives in
diagnosis and therapy. Cancer Metastasis Rev. 2014 Sep;33(2-3):823-32. doi:
10.1007/s10555-014-9506-4. Review. PubMed PMID: 24984804.
7: Lupia A, Peppicelli S, Witort E, Bianchini F, Carloni V, Pimpinelli N, Urso
C, Borgognoni L, Capaccioli S, Calorini L, Lulli M. CD63 tetraspanin is a
negative driver of epithelial-to-mesenchymal transition in human melanoma cells.
J Invest Dermatol. 2014 Dec;134(12):2947-56. doi: 10.1038/jid.2014.258. PubMed
PMID: 24940653. (Co-corresponding)
8: Peppicelli S, Bianchini F, Torre E, Calorini L. Contribution of acidic
melanoma cells undergoing epithelial-to-mesenchymal transition to aggressiveness
of non-acidic melanoma cells. Clin Exp Metastasis. 2014 Apr;31(4):423-33. doi:
10.1007/s10585-014-9637-6. PubMed PMID: 24469963.
9: Peppicelli S, Bianchini F, Contena C, Tombaccini D, Calorini L. Acidic pH via
NF-κB favours VEGF-C expression in human melanoma cells. Clin Exp Metastasis.
2013 Dec;30(8):957-67. doi: 10.1007/s10585-013-9595-4. PubMed PMID: 23784694.
10: Bianchini F, Cini N, Trabocchi A, Bottoncetti A, Raspanti S, Vanzi E, Menchi
G, Guarna A, Pupi A, Calorini L. ¹²⁵I-radiolabeled morpholine-containing
arginine-glycine-aspartate (RGD) ligand of αvβ₃ integrin as a molecular imaging
probe for angiogenesis. J Med Chem. 2012 Jun 14;55(11):5024-33. doi:
10.1021/jm2016232. PubMed PMID: 22621422.
Previous research experiences Prof. Lido Calorini, starting from his PhD Thesis, has spent a great effort studying in vivo behaviour of various tumor cells with different metastatic potential, starting from the first well known model of murine B16-F1/F10 melanoma cells, isolated by I.J. Fidler (MD Anderson Cancer Center, University of Texas). Using these models, he found that metastatic cells express a lipid profile characterized by a reduction of polyunsaturated fatty acids (PUFAs), an increase content of oleic acid and arachidonic acid-enriched-ether-linked lipids. Further, Prof. Calorini demonstrated that metastatic diffusion of tumor cells is significantly reduced in animals fed an essential fatty acid-deficient diet or a diet enriched in n-3 PUFAs, identifying a potential tool to inhibit metastases. Thus, metastatic dissemination is not only the consequence of properties acquired by tumor cells (the so-called “pentathlon’s athlete” theory) but also results from tumor cell/host cell interactions. During a three-year sojourn in the U.S. (Tufts University, Boston, MA), he approached the study of the role of MHC class I antigens in metastatic diffusion of murine melanoma cells and proved that these antigens may influence metastatic dissemination also using mechanisms independent of their involvement in immune reactions. This disclose new role of MHC class I antigens in tumor progression. Thereafter, Prof. Calorini focused his scientific interest to study communication between inflammatory cells of tumor microenvironment and cancer cells. Prof. Calorini investigated the role played by tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs) and their products (inflammatory cytokines, proteases and bioactive lipids) in tumor progression and metastatic dissemination. This interest led to conclude that TAMs activated by melanoma cells themselves promote adhesiveness, invasiveness and metastatic diffusion in target organs realising IFNg and TNFa. This is one of the first observation linking TAMs to IFNg release. Using an experimental model made by prostatic adenocarcinoma cells and fibroblasts isolated from a tumor-bearing prostate gland, he observed that CAFs elicited in prostate cancer cells an aggressive phenotype characterized by an epithelial-to-mesenchymal transition program and stem cell markers. To enrich its experience in in vivo procedure useful to investigate tumor growth and dissemination, Prof. Calorini investigated the biological effects exerted by antagonists of RGD integrins on melanoma-bearing immunodeficient animals using a micro Positron Emission Tomography analysis.
Main scientific contributions
- Non-immunogical role of MHC in cancer
-Tumor-associated macrophages and metastatic dissemination of melanoma cells
- Intratumoral fibroblasts and prostate carcinoma cell progression
- Low pH of tumor microenvironment and melanoma progression to malignancy
- Metabolic reprogramming of cancer cells grown in acidosis
- RGD antagonists and PET imaging of melanoma
- RGD nanocarries and delivery targeted agents in melanoma
Prof. Soldano Ferrone, Massachusetts General Hospital, Harvard Medical School, Boston
Prof. Franca Zanardi, Università degli Studi di Parma, Dipartimento di Scienze degli Alimenti e del Farmaco
Prof. Alberto Pupi, Università degli Studi di Firenze, Dipartimento di Scienze Biomediche Sperimentali e Cliniche, sez. Medicina Nucleare
Prof. Gerardino D’Errico, Università degli Studi di Napoli Federico II, Dipartimento di Scienze chimiche.
Dott. Andrea Trabocchi, Università degli Studi di Firenze, Dipartimento di Chimica.