The Bv8/Prokineticins (PKs) are a new family of peptides identified in frog, fish, reptiles and mammals that signal through two highly homologous G-protein coupled receptors, PKR1 and PKR2. Over the past few years, several biological functions of Bv8/PK proteins have been elucidated. The high expression level of human Bv8/PK2 in bone marrow, lymphoid organs and leukocytes suggested an involvement of these peptides in hematopoiesis and in inflammatory and immunomodulatory processes. Neutrophils are the main endogenous source of Bv8/PK2, while G-CSF is the the only cytokine able to activate PK2 expression in neutrophiles. Moreover G-CSF derived pain seems to be stronlgly related to blood levels of Bv8/PK. According to these results, we started a clinical experimental trial in order to explore role and expression of Bv8/PK proteins in patients treated with chemotherapy for early breast cancer and receiving G-CSF (filgrastim vs peg-filgrastim), investigating also the relationship with G-CSF related pain. Methods: 20 BC pts were submitted to adjuvant FEC100. G-CSF was given as primary prophylaxis. 12 pts received Lenograstim (L: 5 doses, beginning 96 hours after CT) while 8 pts received Pegfilgrastim (P: 1 dose 24 hours after CT). Real-Time PCR and Elisa test were used to analyze Bv8/PK2 expression both in pts receiving L and P. Blood samples for Bv8/PK2 analysis were taken in different steps and days, in order to evaluate Bv8/PK2 expression according to CT time and G-CSF administration. Incidence of neutropenia (N), ○ Previous febrile-N and BP (NRS) were evaluated in all CT cycles. 6 healthy women were recruited as controls to evaluate their Bv8/PK2 basal level. Results: An impressive increase of Bv8/PK2 expression was observed both in L and P group. N occurred in 41.6% of pts treated with L (G3: 8.3%; G4: 16.7%) and in 75% of pts with P (G3: 12.5%; G4: 62.5%; 1 FN). In pts receiving L an incidence of BP occurred in 59.3% (NRS 7-8: 41%) with a mean duration of 6 days; in P group incidence was 37.5% (NRS 7-8: 37.5%), BP lasting 4 days. In all pts BP started within 24-48 hours after G-CSF administration, concurrently with Bv8/PK2 overexpression. Conclusions: Our preliminary results suggest an emerging role of Bv8/prokineticin system in occurrence of G-CSF related BP in primary prevention of CT induced N. Therefore, inhibition of Bv8/PK2 activity should constitute a promising therapeutic strategy to prevent inflammatory pain and perhaps other cancer characteristics.
Abstract 1437: Relationship of G-CSF related bone pain (BP) with Bv8/PK2 expression in breast cancer (BC) patients (pts) treated with FEC100 adjuvant chemotherapy (CT) / Rossi, Luigi; Papa, Anselmo; Tomao, Federica; Negri, Lucia; Tomao, Silverio. - In: CANCER RESEARCH. - ISSN 0008-5472. - STAMPA. - 76:(2016), pp. 1437-1437. ((Intervento presentato al convegno AACR 107th Annual Meeting 2016 tenutosi a New Orleans, LA nel April 16-20, 2016 [10.1158/1538-7445.AM2016-1437].