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Pancreatic Cancer Requires HSP70 in the Tumor Microenvironment for Cancer Growth
Abstract   Peer reviewed

Pancreatic Cancer Requires HSP70 in the Tumor Microenvironment for Cancer Growth

Bhuwan Giri, Bharti Garg, Vrishketan Sethi, Shrey Modi, Sulagna Banerjee, Sundaram Ramakrishnan, Ashok Saluja and Vikas Dudeja
Journal of the American College of Surgeons, Vol.225(4), pp.e124-e125
10/2017
DOI: 10.1016/j.jamcollsurg.2017.07.861

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Abstract

INTRODUCTION: Heat shock proteins (HSPs) act as chaperones for cells during distress. While it is known that cancer cells hijack this machinery and inhibiting HSP70 in cancer cells results in decreased proliferation, role of HSP70 in tumor microenvironment (TME) is unknown. We aim to find out if HSP70 in the TME modulates cancer growth. METHODS: Cancer cells derived from KPC (Pdx1-Cre; K-Ras+/LSLG12D; p53R172H/+) or B16:F10 cell line were implanted orthotopically in mice with deletion of Hspa1a and Hspa1b (Hsp70−/−) or their wild type (WT) littermate controls. This simulated a scenario where cancer cells had intact HSP70 but HSP70 was absent in TME. Pancreatic-stellate-cells (PSCs) from Hsp70−/− or WT mice were co-injected with KPC cells in WT (ratio=9:1) mice to evaluate the effect of absent HSP70 in tumor stroma specifically. Cell mediated cytotoxicity was assessed after splenocytes from tumor immunized mice were co-incubated with cancer cells. RESULTS: Tumors derived from both KPC and B16-F10 cells were smaller in Hsp70−/− mice suggesting that the absence of HSP70 in TME decreased tumor growth. KPC cells co-injected with WTPSC or HSP70-/-PSC did not show any difference in tumor size hinting that the inhibitory effect of lack of HSP70 in TME may not be stroma dependent. Subsequently, co-incubation of HSP70-/- splenocytes with KPC cells led to greater cell mediated cytotoxicity when compared to WT splenocytes. CONCLUSIONS: The absence of HSP70 in the TME inhibits tumor growth possibly by enhancing immune mediated cytotoxicity. HSP70 inhibition in immune compartment of TME could emerge as a novel therapeutic strategy against cancer.

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